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Timing of Peak Bone Mass: Discrepancies between CT and DXA
Abstract
The time of life in which peak bone mass in the axial skeleton is attained has been the subject of considerable controversy, with estimates ranging from the time of sexual and skeletal maturity to the fifth decade of life.
The objective was to examine whether dual energy x-ray absorptiometry (DXA) and computed tomography (CT) values for bone mass and bone density (BD) in the axial skeleton increase after sexual and skeletal maturity.
Measurements of vertebral bone mineral density and bone mineral content (BMC) by DXA and vertebral BD and BMC by CT were obtained in 50 sexually and skeletally mature white females at baseline and 3 yr later. CT BMC values were calculated through analysis of vertebral volume in relation to density (BMC = vertebral volume x BD).
Although neither CT BD nor BMC measures changed with time, DXA bone mineral density and BMC values were significantly higher at follow-up (P < 0.0001). Despite strong correlations between DXA and CT bone measures, DXA yielded greater changes in bone values in 47 of 50 subjects.
Bone acquisition in the lumbar spine as measured by CT reaches its peak by sexual and skeletal maturity. In contrast, bone values by DXA continue to increase after puberty and cessation of longitudinal growth. Increases in DXA measures are likely a reflection of inhomogeneous changes in soft tissues around the spine or of disproportionate increases in the posterior elements of the vertebrae rather than of changes within the vertebral body.
... But by the end of pubertal maturation there is no significant gender difference in the volumetric trabecular density. 2 PBM is reached at the end of the twenties, which makes childhood and teenage years the best time for bone growth, although this is a controversial period. 3 The adult human skeleton is composed of 80% cortical bone and 20% trabecular bone. Different bones and skeletal sites within bones have different ratios of cortical to trabecular bone. ...
... 26,27 Using QCT, the PBM seems to be reached with sexual maturity, and with DXA it is observed a rise after the longitudinal growth ceases. 3 It is crucial to have a diagnosis tool reliable and effective to determine bone health, osteopenia, or osteoporosis in pediatric patients. Plus, there is no reference value for vBMD classification by age and gender for Mexican pediatric population. ...
... Age group (years) n BMI ± SD (mg/cm 2 ) vBMD ± SD (mg/cm 2 ) Increment intergroup SD (mg/cm 3 Table 1 shows the mean and standard deviation values for BMI and vBMD values for Mexican female and male pediatric population, for age groups from two to 25 years old. The BMI for both genders ranges from 13.75 to 28.73 kg/m 2 , which are within the normal limits. ...
... During childhood and adolescence, bone mass increases till a plateau is reached, the peak bone mass. The age at which peak bone mass is attained may vary according to sex, type of measurement (dual energy X-ray absorptiometry (DXA) or computed tomography (CT)), and skeletal site [1][2][3][4]. CT measurements showed that vertebral bone mineral content (BMC) and bone mineral density (BMD) reached their peak around the time of sexual maturity and cessation of longitudinal growth in females [1]. ...
... The age at which peak bone mass is attained may vary according to sex, type of measurement (dual energy X-ray absorptiometry (DXA) or computed tomography (CT)), and skeletal site [1][2][3][4]. CT measurements showed that vertebral bone mineral content (BMC) and bone mineral density (BMD) reached their peak around the time of sexual maturity and cessation of longitudinal growth in females [1]. Studies using DXA reported that peak lumbar spine volumetric BMD was attained in girls around 16 years and in boys around 18 years [3,5]. ...
... Studies using DXA reported that peak lumbar spine volumetric BMD was attained in girls around 16 years and in boys around 18 years [3,5]. Areal BMD may increase till a later age because certain bones continue to increase in size [1,4,6]. About 85-90% of final adult bone mass is acquired by the age of 18 years in girls and 20 years in boys [4]. ...
During childhood and adolescence, bone mass and lean body mass (LBM) increase till a plateau is reached. In this longitudinal and cross-sectional study, the age of reaching the plateau was evaluated for lumbar spine and total body bone mass measurements and lean body mass. The association between fractures and bone mineral density (BMD) was studied.
We included 501 healthy participants, 141 males and 360 females, aged 13-29 years. Of these 90 had participated in a previous longitudinal study of 444 participants, aged 4-20 years (for the first measurement) and 198 participants, aged 8-25 years (for a second measurement). BMD and body composition were measured with dual energy X-ray absorptiometry (DXA). Volumetric BMD (bone mineral apparent density, BMAD) was calculated. All the data were used to determine the age of reaching the plateau.
The plateau for lumbar spine BMD, BMAD, total body BMD, bone mineral content and LBM was reached between 18 and 20 years of age in females and between 18 and 23 years in males. The prevalence of fractures was 37% in males and 28% in females. Total body BMD Z-score was significantly lower in all participants who had had a fracture (p<0.05), whereas lumbar spine BMD and BMAD was only significantly lower in females who had had fractures (p=0.007 and p<0.001, respectively). Mean lumbar spine BMAD Z-score at the previous measurement was significantly lower in the participants who had a first fracture between the last two measurements (p=0.04).
Peak BMD and peak LBM were attained between 18 and 20 years in females and between 18 and 23 years in males in this study using longitudinal and cross sectional data in the age range of 4 to 30 years. A significantly lower total body BMD was seen in participants who had had a fracture and a lower lumbar spine BMD and BMAD in females who had had a fracture. Lumbar spine BMAD Z-score seems to be a good predictor for future fractures.
... During the pubertal stage, bone parameters change at a significant rate, and by the end of puberty, bone mass reaches almost the full PBM characteristic of an adult [15]. Findings suggest that PBM is not achieved across the skeleton at the same rate, Wren et al. in 2007 suggest that PBM in the lumbar spine has optimal values already at the end of sexual maturation [16], while others demonstrated that bone mineral accrual and PBM at the spine occurs around age 30 years or later. Another study showed hip PBM has been noted to occur between age 16 and 19 years in women [4]. ...
... During the pubertal stage, bone parameters change at a significant rate, and by the end of puberty, bone mass reaches almost the full PBM characteristic of an adult [15]. Findings suggest that PBM is not achieved across the skeleton at the same rate, Wren et al. in 2007 suggest that PBM in the lumbar spine has optimal values already at the end of sexual maturation [16], while others demonstrated that bone mineral accrual and PBM at the spine occurs around age 30 years or later. Another study showed hip PBM has been noted to occur between age 16 and 19 years in women [4]. ...
Background
During childhood and adolescence, skeletal microarchitecture and bone mineral density (BMD) undergo significant changes. Peak bone mass is built and its level significantly affects the condition of bones in later years of life. Understanding the modifiable factors that improve bone parameters at an early age is necessary to early prevent osteoporosis. To identify these modifiable factors we analysed the relationship between dairy product consumption, eating habits, sedentary behaviour, and level of physical activity with BMD in 115 young boys (14–17 years).
Methods
Bone parameters were measured by dual energy x-ray absorptiometry using paediatric specific software to compile the data. Dairy product consumption and eating habits were assessed by means of a dietary interview. Sedentary behaviour and physical activity was assessed in a face-to-face interview conducted using the International Physical Activity Questionnaire. Data collection on total physical activity level was performed by collecting information on the number of days and the duration of vigorous and moderate intensity (MVPA) and average daily time spent in sitting (SIT time).
Results
The strongest relationships with BMD in distal part of forearm were found for moderate plus vigorous activity, sit time, and intake of dairy products, intake of calcium, protein, vitamin D, phosphorus from diet. Relationships between BMD, bone mineral content (BMC) in the distal and proximal part of the forearm and PA, sit time and eating parameters were evaluated using the multiple forward stepwise regression. The presented model explained 48–67% (adjusted R² = 0.48–0.67; p < 0.001) of the variance in bone parameters. The predictor of interactions of three variables: protein intake (g/person/day), vitamin D intake (µg/day) and phosphorus intake (mg/day) was significant for BMD dis (adjusted R² = 0.59; p < 0.001). The predictor of interactions of two variables: SIT time (h/day) and dairy products (n/day) was significant for BMD prox (adjusted R² = 0.48; p < 0.001). Furthermore, the predictor of interactions dairy products (n/day), protein intake (g/person/day) and phosphorus intake (mg/day) was significant for BMC prox and dis (adjusted R² = 0.63–0.67; p < 0.001).
Conclusions
High physical activity and optimal eating habits especially adequate intake of important dietary components for bone health such as calcium, protein, vitamin D and phosphorus affect the mineralization of forearm bones.
... Peak bone acquisition and strength of the vertebral body are greater in men than in women, which is mainly the consequence of the larger male vertebra since differences in vertebral bone density are less striking or nonexistent [4,78]. Both vertebral bone density and vertebral CSA by CT reach their highest values around the time of sexual maturity and cessation of longitudinal growth [79,80] (Fig. 4). These findings are consistent with previous histological examinations of the vertebrae and/or iliac crest showing the loss of cancellous bone as early as the third decade of life [81,82]. ...
... These findings are consistent with previous histological examinations of the vertebrae and/or iliac crest showing the loss of cancellous bone as early as the third decade of life [81,82]. They are also in agreement with anatomical studies showing that little if any bone is gained from the periosteal surface of vertebral bone in adult women and that the overall CSA of their vertebrae remain relatively stable [79,83]. ...
A high priority in imaging-based research is the identification of the structural basis that confers greater risk for spinal disorders. New evidence indicates that factors related to sex influence the fetal development of the axial skeleton. Girls are born with smaller vertebral cross-sectional area compared to boys—a sexual dimorphism that is present throughout life and independent of body size. The smaller female vertebra is associated with greater flexibility of the spine that could represent the human adaptation to fetal load. It also likely contributes to the higher prevalence of spinal deformities, such as exaggerated lordosis and progressive scoliosis in adolescent girls when compared to boys, and to the greater susceptibility for spinal osteoporosis and vertebral fractures in elderly women than men.
... Bone growth is greatest during childhood and adolescence, with longitudinal growth completed by the late teens to early twenties [24]. Bone continues to grow appositionally until the mid-tolate twenties, when peak bone mass is attained [25]. ...
... PBM is generally considered to be achieved during the second or third decade of life, but the exact timing is site-and gender-dependent. Some longitudinal studies have suggested that PBM at the lumbar spine is achieved by the end of sexual maturation in both men and women, (17, 18) whereas others showed that bone mineral accrual at this site continues into the third decade or even later. (19-21) Likewise, achievement of PBM at the hip has been suggested to occur between age 16 and 19 years in women, (20) whereas studies in men have shown either decreases (20-22) or increases (17) in hip areal BMD during the third decade of life. ...
This narrative review discusses several aspects of the management of osteoporosis in patients under 50 years of age. Peak bone mass is genetically determined but can also be affected by lifestyle factors. Puberty constitutes a vulnerable period. Idiopathic osteoporosis is a rare, heterogeneous condition in young adults due in part to decreased osteoblast function and deficient bone acquisition. There are no evidence-based treatment recommendations. Drugs use can be proposed to elderly patients at very high risk. Diagnosis and management of osteoporosis in the young can be challenging, in particular in the absence of a manifest secondary cause. Young adults with low bone mineral density (BMD) do not necessarily have osteoporosis and it is important to avoid unnecessary treatment. A determination of BMD is recommended for premenopausal women who have had a fragility fracture or who have secondary causes of osteoporosis: secondary causes of excessive bone loss need to be excluded and treatment should be targeted. Adequate calcium, vitamin D, and a healthy lifestyle should be recommended. In the absence of fractures, conservative management is generally sufficient, but in rare cases, such as chemotherapy-induced osteoporosis, antiresorptive medication can be used. Osteoporosis in young men is most often of secondary origin and hypogonadism is a major cause; testosterone replacement therapy will improve BMD in these patients. Diabetes is characterized by major alterations in bone quality, implying that medical therapy should be started sooner than for other causes of osteoporosis. Primary hyperparathyroidism, hyperthyroidism, Cushing’s syndrome and growth hormone deficiency or excess affect cortical bone more often than trabecular bone.
... Despite the deteriorations in the years after GH cessation, average BMD TB and BMAD LS at 5 years after GH cessation were above 21 SDS, and only a small percentage of all subjects had a BMD TB or BMAD LS below 22 SDS, which is reassuring. Most of the skeletal mass in the total body and lumbar spine is attained in the first years of the third decade (28,30,31). This attained peak bone mass is an important determinant of osteoporosis in later life (8). ...
Context
Short children born small for gestational age (SGA) have a bone mineral density (BMD) below average. Growth hormone (GH) treatment improves height and BMD in short SGA children. Longitudinal data on BMD in adults born SGA, after GH cessation, are lacking.
Objectives
To determine BMD in young adults born SGA during 5yrs after GH cessation.
Methods
In 173 GH-treated adults born SGA (SGA-GH), BMD of total body (BMDTB) and bone mineral apparent density of lumbar spine (BMADLS) were measured longitudinally at adult height (GH-stop), and 6 months, 2yrs and 5yrs thereafter. At 5yrs after GH-stop (age 21yrs), data were compared with 45 untreated short SGA adults (SGA-S), 59 SGA adults with spontaneous catch-up (SGA-CU), and 81 adults born appropriate for gestational age (AGA).
Results
At GH-stop (mean age 16.4yrs), estimated mean (SE) BMDTB SDS was -0.40 (0.1) in males and -0.51 (0.1) in females followed by a trend towards a decrease of BMDTB in males to -0.59 (0.1) at 5yrs after GH-stop (p=0.06), while it remained stable in females (-0.57 (0.1), p=0.33). At GH-stop, BMADLS SDS was -0.01 (0.1) in males and -0.29 (0.1) in females, followed by a decrease in males and females to -0.38 and -0.55 at 5yrs after GH-stop, resp. (p<0.001). At 5yrs after GH-stop, BMDTB and BMADLS in SGA-GH were similar compared to SGA-S, SGA-CU and AGA.
Conclusion
After cessation of GH-treatment, there is a gradual decline of BMADLS, but at the age of 21yrs, BMDTB and BMADLS are similar as in untreated short SGA adults.
... 10,11 In the axial skeleton, bone acquisition reaches peak values at the time of sexual and skeletal maturity and reported increases in DXA measures of bone are likely due to the influence of soft tissues, rather than to changes in bone acquisition within the vertebral body. 12 Thus, the timing of PBM is dependent upon the skeletal site and bone compartment under consideration, sex, maturational timing, and lifestyle factors. ...
... Furthermore, if muscle was a causal factor during bone development, then increased muscle mass and muscle strength should precede the majority of bone mineral accrual. While such a sequential relationship has been observed using twodimensional DXA 9 , three-dimensional CT data show that bone mineral accrual may cease before peak muscle strength is reached 10 . At the other end of the spectrum, age-related sarcopenia reduces muscle loading of bone and, therefore, should induce bone loss. ...
Little is known about interactions between muscle and bone during the removal and application of mechanical signals. Here, we applied 3wk of hindlimb unloading followed by 3wk of reambulation to a genetically heterogeneous population of 352 adult mice and tested the hypothesis that changes in muscle are associated with changes in bone at the level of the tissue and the genome. During unloading and relative to normally ambulating control mice, most mice lost muscle and cortical bone with large variability across the population. During reambulation, individual mice regained bone and muscle at different rates. Across mice, changes in muscle and trabecular/cortical bone were not correlated to each other during unloading or reambulation. For unloading, we found one significant quantitative trait locus (QTL) for muscle area and five QTLs for cortical bone without overlap between mechano-sensitive muscle and cortical bone QTLs (but some overlap between muscle and trabecular QTLs). The low correlations between morphological changes in muscle and bone, together with the largely distinct genetic regulation of the response indicate that the premise of a muscle-bone unit that co-adjusts its size during (un)loading may need to be reassessed. © 2016, International Society of Musculoskeletal and Neuronal Interactions. All rights reserved.
... These discrepant results likely reflect the limitations of the techniques employed. Changes in body composition influence DXA measures during growth, and peripheral quantitative CT measures in children have poor reproducibility due to large variations in bone growth (167,168). Confounding effects associated with growth and development are common when studying sexually and skeletally immature young women, using DXA or CT. ...
In this review, we will first discuss the concept of bone strength and introduce how fat at different locations, including the bone marrow, directly or indirectly regulates bone turnover. We will then review the current literature supporting the mechanistic relationship between marrow fat and bone and our understanding of the relationship between body fat, body weight, and bone with emphasis on its hormonal regulation. Finally, we will briefly discuss the importance and challenges of accurately measuring the fat compartments using non-invasive methods. This review highlights the complex relationship between fat and bone and how these new concepts will impact our diagnostic and therapeutic approaches in the very near future.
... Many of the discrepancies in the current literature may be due to results from cross-sectional compared with longitudinal data, inadequate methods used to control for differences in biological age, and failure to account for the influence of changes in body composition. For example, errors in DXA measures of BMC due to inhomogenous fat mass distribution may lead researchers to conclude that bone mass continues to increase well into adulthood [36]. ...
Adolescence is a crucial period during which skeletal development lays the foundation for bone health in adulthood. With recent advancements in bone imaging technology we now know that profound increases in bone mass during adolescence are associated with important changes in bone macro- and microstructure that influence bone strength accrual. In this chapter, we summarize current literature that describes bone acquisition during adolescence, and in doing so, we focus on studies that utilized three-dimensional imaging tools such as peripheral quantitative computed tomography. In addition, we provide an overview of the functional model of bone development and mechanical (e.g. physical activity) and nonmechanical (e.g. hormones) factors known to influence bone development.
... Auf jeden Fall ist die Mehrzahl der Belastungen sehr gering (bis 10 µStrain), hohe Belastungen jenseits 1000 µStrain sind sehr selten [10]. [15,16], andere Untersuchungen stellen die Bedeutung der Muskelkraft zugunsten der Schwerkraft eher in den Hintergrund [17,18]. Die Datenlage ist somit noch nicht konklusiv. ...
To fulfil its mechanical function, bone must adapt to the mechanical loads through control of bone mass and strength. While disuse and inactivity reduce bone mass, strenuous exercise does increase it. Physical activity loads the muscular-skeletal system and these intermittent compressive forces cause deformation of the bone and fluid flow in the lacunocanalicular system. Osteocytes are sensitive to this shear stress. The mechanical forces are converted into biochemical signals; this process is known as mechanotransduction. Via transmission the effector cells are activated. If the deformation of the bone exceeds a certain threshold (modelling threshold), osteoblasts add bone and increase its strength. On the other hand, if a lower remodelling threshold is not regularly exceeded, bone is removed by osteoclasts. This control loop is not only dependent on the intensity and frequency of physical activity, but also on the acceleration of movement. Additionally, non-mechanical factors like the hormone status modulate the intensity of bone adaptation.
... Although capacity to maintain musculoskeletal function is among one of the strongest determinants of health aging and musculoskeletal conditions in the pediatric population are an emerging public health concern, few studies have investigated the impact of obesity on strengthstructural properties of the musculoskeletal system. Previous studies have examined associations between body composition (by DXA) and qualitative assessment (via pQCT) measures in adolescents, but few have included obese participants [7][8][9] and one included only males [10]. These studies demonstrated a positive correlation between stress strain index (SSI) and total body fat mass in healthy weight children. ...
Recent studies have challenged the traditionally accepted view that obesity is beneficial to the growing skeleton. Despite having greater bone mineral content (BMC) and lean mass when assessed by dual X-ray energy absorptiometry (DXA), compromise in skeletal integrity (i.e. fracture, joint pain) are increasingly being reported in the pediatric population. The objective of this study was to evaluate the relationship between absolute quantitative (mass) and qualitative aspects of bone and muscle (cortical and trabecular density, muscle and marrow density, and stress strain index; SSI) in obese peri-pubertal girls ages 7-11 years. Mass (bone, fat and lean) was assessed by DXA and density, strength and fatty infiltration was evaluated by peripheral quantitative computed tomography (pQCT). pQCT scans were performed at 4% and 66% of radius length as well as 66% of the tibia length. All girls were obese BMI % (>95th). Statistical analysis was conducted using the sample mean body fat percentage girls to stratify into two groups, obese ( 43.78 %). BMC and lean mass were not significantly different between the groups. Total body fat was positively associated with both lean and bone mass in both groups. Total body fat was inversely associated with cortical density and SSI in the upper and lower extremity. SSI at 4% in the radius was significantly lower in the morbidly obese group, yet the trabecular and cortical density of the upper extremity was higher. In addition, marrow area was greater yet marrow density, an estimate of bone marrow adipose tissue was significantly lower in the morbidly obese group (p<0.05). This study extends these observations to demonstrate the impact of obesity in the context of bone and muscle quality and suggest the increased fracture in obese, particularly morbidly obese girls, rates may be due to the adverse impact of obesity on musculoskeletal health.
... 13 Knowledge that little if any bone is gained from the periosteal surface of vertebral bone in adult women and that the overall CSA of their vertebrae remain relatively stable underscore the importance of early variations in vertebral growth. 22,23 Whereas sex was found to have a significant effect on intrauterine development of the axial skeleton, values for humeral CSA did not differ between boys and girls at birth. This finding is consistent with existing data in children and adolescents showing that the cross-sectional dimensions of the appendicular and axial skeletons are influenced by separate determinants. ...
To examine whether the sex-related differences in vertebral cross-sectional area (CSA) found in children and at the timing of peak bone mass-a major determinant of osteoporosis and future fracture risk-are also present at birth.
Vertebral CSA, vertebral height, and intervertebral disc height were measured using magnetic resonance imaging in 70 healthy full-term newborns (35 males and 35 females). The length and CSA of the humerus, musculature, and adiposity were measured as well.
Weight, body length, and head and waist circumferences did not differ significantly between males and females (P ≥ .06 for all). Compared with newborn boys, girls had significantly smaller mean vertebral cross-sectional dimensions (1.47 ± 0.11 vs 1.31 ± 0.12; P < .0001). Multiple linear regression analysis identified sex as a predictor of vertebral CSA independent of gestational age, birth weight, and body length. In contrast, the sexes were monomorphic with regard to vertebral height, intervertebral disc height, and spinal length (P ≥ .11 for all). There were also no sex differences in the length or cross-sectional dimensions of the humerus or in measures of musculature and adiposity (P ≥ .10 for all).
Factors related to sex influence fetal development of the axial skeleton. The smaller vertebral CSA in females is associated with greater flexibility of the spine, which could represent the human adaptation to fetal load. Unfortunately, it also imparts a mechanical disadvantage that increases stress within the vertebrae for all physical activities and increases the susceptibility to fragility fractures later in life.
Copyright © 2015 Elsevier Inc. All rights reserved.
... Earlier studies using DXA have suggested that bone mass peaks long after sexual and skeletal maturity, potentially into an individual's third decade or beyond (16,17). Other studies indicate that bone mass peaks earlier than is currently believed (18,19). This lack of consensus arises from the paucity of long-term serial data, the use of cross-sectional data, and inconsistencies in accounting for potential risk factors. ...
The literature has not reached a consensus on the age when peak bone mass is achieved. This study examines growth patterns of total bone mineral content (TBMC) and total bone mineral density (TBMD), peak bone mass, effect of concurrent anthropometry measures, and physical activity on growth patterns in a sample of 312 white males and 343 females aged 8–30 yr. We analyzed data from participants enrolled in Fels Longitudinal Study. Descriptive analysis was used to ascertain characteristics of participants and growth patterns of TBMC and TBMD. Mixed effects models were applied to predict ages at attainment of peak TBMC and TBMD and assess the effects of height, weight, body mass index (BMI), and habitual physical activity on the attainment. Significant differences between sexes were observed for measures of TBMC and TBMD, and differences varied with age. For females, predicted median ages at peak TBMC and TBMD attainments are 21.96 yr (interquartile range [IQR]: 21.81–22.21) and 22.31 yr (IQR: 21.95–22.59), respectively. For males, predicted median ages are 23.34 yr (IQR: 24.34–26.19) and 26.86 yr (IQR: 25.14–27.98) respectively. For females, height, weight, and BMI, but not physical activity, had significant influences on attainment of TBMC and TBMD (p < 0.01). For males, weight and BMI, but not height and physical activity, exerted significant influence on attainment of TBMC and TBMD (p < 0.01), and also modified correlations between age and peak TBMC and TBMD. Our results suggest that (1) for both sexes, trajectories of TBMC and TBMD follow a curvilinear pattern between ages 8 and 30 yr; (2) predicted ages at peak TBMC and TBMD are from early to late 20s for both white males and females, with females reaching their peaks significantly earlier than males; and (3) concurrent height, weight, and BMI, but not habitual physical activity, exert significant effects on trajectories of TBMC and TBMD.
... Timing of PBM and peak areal bone mineral density (aBMD) has mainly been assessed using dual x-ray absorptiometry (DXA). However, age of PBM varies according to sex, measurement tool, and skeletal site measured [3][4][5][6][7]. For example, using DXA, hip aBMD generally peaks before lumbar spine [8,9], and aBMD at both sites peaks in females before males [3,5]. ...
Within a normative youth cohort (16–29 years) bone parameters for males and females remained stable at the radius. At the tibia, a peak was observed for females at 16–19 years, with bone density and strength decreasing by 29 years.
Purpose
To determine if bone microstructural and strength parameters identified by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) at the distal radius and tibia, peak within the age range of this youth cohort, and whether the timing of the peaks differ based on sex or skeletal site.
Methods
We recruited 251 participants (158 female; 16 to 29 years), grouping them into 5-year age brackets (16–19; 20–24; 25–29 years) assessing microstructural and strength parameters with HR-pQCT and FEA.
Results
HR-pQCT assessment of males and females (age-matched groups) showed males had higher total area and BMD, trabecular BMD and trabecular number (radius only) cortical thickness and porosity, and failure load, but lower cortical BMD (p
... 17 We have also shown recently in the same cohort that bone mass during childhood is a predictor of pediatric fractures. 18 Although the time of life when DXA values reach their peak has been of considerable controversy, 19,20 most estimates indicate that bone mass does not significantly increase after the third decade. 5 Because the degree of tracking during young adulthood should be comparable or greater than during growth, the findings of our study underscore the potential of these measures to predict bone mineral status in older adulthood. ...
... Exclusion criteria included infants of mothers with a history of gestational diabetes or hypertension in pregnancy, malabsorption syndromes (celiac and CrohnÕs disease), or taking medications that interfere with vitamin D metabolism (anticonvulsants and corticosteroids). Mothers taking $50 mg/d of vitamin D from supplementation were not included, because this value is above the current nutrition recommendations (22). Demographic information, including race, education, and income (in Canadian dollars), was reported by the mother. ...
The biological equivalency of ergocalciferol (D2) and cholecalciferol (D3) has been debated; several comparisons have appeared in the adult literature but are scarce in pediatrics. The objective of this study was to compare increases in plasma 25-hydroxyvitamin D [25(OH)D] concentrations and attainment of 50 and 75 mol/L status cutoffs following 3 mo of daily supplementation with D2 compared with D3. Healthy, breast-fed, 1-mo-old infants (n = 52) received 10 μg (400 iu) of either D2 or D3 daily. At 1 and 4 mo of age, plasma 25-hydroxyergocalciferol and 25-hydroxycholecalciferol concentrations were determined by liquid chromatography tandem MS (LC-MS/MS) and total 25(OH)D by chemiluminescent immunoassay (DiaSorin Liaison). Data were analyzed using t tests and χ(2) by intent to treat. A total of 23% of infants were deficient (≤24.9 nmol/L) at baseline and 2% at follow-up on the basis of LC-MS/MS. At 4 mo, 96% were breastfed and there were no differences in compliance, breastfeeding rates, or sun exposure among groups. The change in total 25(OH)D measured by LC-MS/MS did not differ between the D2 (17.6 ± 26.7 nmol/L) and D3 (22.2 ± 20.2 nmol/L) groups. In the combined groups, the baseline plasma 25(OH)D concentration was inversely related to the change in total 25(OH)D (r = -0.52; P < 0.001). Overall, 86% of infants met the 50 nmol/L cutoff at follow-up; however, fewer infants in the D2 group (75%) met this level compared with the D3 group (96%) (P < 0.05). Similar results were obtained by immunoassay. In conclusion, the increase in the 25(OH)D concentration among the D2 and D3 groups did not differ, suggesting daily intake of either isoform is acceptable for infants <4 mo.
... While we cannot explain the discrepancy with our data it may reflect the use of DEXA versus micro-CT to determine bone mass. DEXA measurements of bone density are influenced by fat distribution (Formica et al., 1995;Hangartner and Johnston, 1990;Tothill et al., 1997;Tothill et al., 1999;Wren et al., 2007), which is potentially affected by IL-17 (Goswami et al., 2009;Shin et al., 2009;Sumarac-Dumanovic et al., 2009). Our conclusions are also supported by the multiple approaches we used to test the role of the IL-17 signaling cascade in the pathogenesis of post-menopausal osteoporosis. ...
Estrogen-deficient osteoporosis may be an inflammatory disorder and we therefore asked if IL-17 participates in its pathogenesis. Deletion of the principal IL-17 receptor (IL-17RA) protects mice from ovariectomy (OVX)-induced bone loss. Further supporting a central role of IL-17 in its pathogenesis, OVX-induced osteoporosis is prevented by a blocking antibody targeting the cytokine. IL-17 promotes osteoclastogenesis by stimulating RANK ligand (RANKL) expression by osteoblastic cells, mediated by the IL-17RA SEFIR/TILL domain. Estrogen deprivation, however does not enhance IL-17RA mRNA expression by osteoblasts or in bone, but augments that of Act1, an IL-17RA-interacting protein and signaling mediator. Similar to IL-17RA(-/-) mice, those lacking Act1 are protected from OVX-induced bone loss. Also mirroring IL-17RA-deficiency, absence of Act1 in osteoblasts, but not osteoclasts, impairs osteoclastogenesis via dampened RANKL expression. Transduction of WT Act1 into Act1(-/-) osteoblasts substantially rescues their osteoclastogenic capacity. The same construct, however, lacking its E3 ligase U-box or its SEFIR domain, which interacts with its counterpart in IL-17RA, fails to do so. Estrogen deprivation, therefore, promotes RANKL expression and bone resorption in association with upregulation of the IL-17 effector, Act1, supporting the concept that post-menopausal osteoporosis is a disorder of innate immunity.
... Wren et al. compared change in lumbar spine (L1-L3) BMC and BMD by QCT and AP DXA over three years in women ages 14 to 20 and found that while BMC and areal BMD by DXA increased, there was no change by QCT [39]. This may represent inaccuracies in the DXA measurement due to changes in soft tissue or the inclusion of posterior vertebral elements. ...
Peak bone mass is an important determinant of bone mass in later life, but the age of peak bone mass is still unclear. We found that bone size and density increase and bone turnover decreases until age 25. It may be possible to influence bone accrual into the third decade.
Peak bone mass is a major determinant of bone mass in later life. Bone growth and maturation is site-specific, and the age of peak bone mass is still unclear. It is important to know the age to which bone accrual continues so strategies to maximise bone mass can be targeted appropriately. This study aims to ascertain the age of lumbar spine peak bone mass.
We measured lumbar spine BMC, estimated volume and BMAD by DXA and biochemical markers of bone turnover in 116 healthy males and females ages 11 to 40, followed up at an interval of five to nine years.
The majority of peak bone mass was attained by the mid-twenties. Increases in BMC in adolescents and young adults were mostly due to increases in bone size. Bone turnover markers decreased through adolescence and the third decade and the decreasing rate of change in bone turnover corresponded with the decreasing rate of change in lumbar spine measurements.
Skeletal maturation and bone mineral accrual at the lumbar spine continues into the third decade.
... PBM is reached before the age of 16 years in girls and around 18 years in boys in most skeletal sites except of the cortices of long bones (Bonjour et al. 1991, Theintz et al. 1992, Lorentzon et al. 2005, although individual and racial differences exist. Many of the discrepancies related to the achievement of PBM are derived from different measurements (Wren et al. 2007). Axial growth ceases as the growth plates in long bones are closed by oestrogens in both genders. ...
D-vitamiini ylläpitää normaalia luun kasvua ja uudistumista koko elämän ajan. Suomessa, kuten monissa muissakin länsimaissa, väestön D-vitamiinitilanne on riittämätön – talvisin osalla jopa puutteellinen. Tässä väitöskirjassa on tutkittu, lisääkö D-vitamiini luumassan kertymistä kasvuiässä, ja ylläpitäkö D-vitamiini luuston tasapainoista aineenvaihduntaa aikuisiällä. Nämä vaikutukset saattavat ehkäisi osteoporoosin kehittymistä eri ikäkausina. Väitöskirjatyössä tutkittiin erisuuruisten D-vitamiinilisäysten vaikutuksia kolmessa eri ikäryhmässä, jotka olivat 11-12 -vuotiaat tytöt (N=228), 21-49 -vuotiaat miehet (N=54) ja 65-85 -vuotiaat naiset (N=52). Tutkittavat satunnaistettiin ryhmiin, jotka nauttivat joko lumevalmistetta tai 5-20 µg D3-vitamiinia vitamiinilisänä. Tutkimukset olivat kaksoissokkoutettuja. Tutkimuksen aikana tutkittavilta otettiin paastoveri- ja virtsanäytteitä. Lisäksi he täyttivät tutkimuslomakkeen taustatietojen kartoittamiseksi sekä frekvenssikyselylomakkeen kalsiumin ja D-vitamiinin saannin selvittämiseksi. Tyttöjen luunmineraalitiheys (BMD) mitattiin DXA–laitteella ja miesten volumetrinen luuntiheys pQCT-menetelmällä. Näytteistä määritettiin mm. seerumin 25-hydroksi-D-vitamiinin (=S-25-OHD), lisäkilpirauhashormonin (=S-PTH) ja luun aineenvaihduntaa kuvaavien merkkiaineiden pitoisuuksia. Murrosikäisten tyttöjen poikkileikkaustutkimuksessa S-25-OHD- ja luun muodostusmerkkiaineen pitoisuudet vaihtelivat kuukausien välillä; suurimmat pitoisuudet mitattiin syyskuussa ja pienimmät maaliskuussa, mikä kuvastaa vuodenaikaisvaihtelua. Vastaava vaihtelu havaittiin lannerangan ja reisiluun BMD:ssä. D-vitamiinilisäyksellä oli myönteinen vaikutus tyttöjen luumassan lisääntymiseen. Suurin D-vitamiinilisä (10 µg/vrk) lisäsi luumassaa 17.2% enemmän reisiluussa ja 12.5% enemmän lannerangassa verrattuna lumevalmistetta nauttivien tyttöjen vastaaviin tuloksiin, mutta tulos riippui hoitomyöntyvyydestä. D-vitamiinin vaikutus luustoon välittyi vähentyneen luun hajotuksen kautta. Tutkimustuloksiin perustuen riittävä D-vitamiinin saanti murrosikäisille tytöille on 15 µg/vrk. D-vitamiinilisän vaikutus 65-85 -vuotiaiden naisten S-25-OHD-pitoisuuteen vakioitui kuudessa viikossa annoksen ollessa 5-20 µg/vrk. Näillä D-vitamiiniannoksilla ei saavutettu tavoiteltavaa S-25-OHD-pitoisuutta, joka on 80 nmol/l. Arvioimme, että 60 nmol/l -pitoisuuden, jota esiintyy kesäisin tämän ikäryhmän suomalaisilla, tämän ikäryhmän naiset saavuttaisivat 24 µg:n päivittäisellä D-vitamiinin saannilla. Terveillä miehillä havaittiin vuodenaikaisvaihtelu S-25-OHD- ja S-PTH-pitoisuudessa sekä luun hajotusta kuvaavassa merkkiainepitoisuudessa. Toisaalta vaihtelua ei havaittu radiuksen volumetrisessä luuntiheydessä eikä luun muodostusmerkkiaineen pitoisuudessa. Vuodenaikaisvaihtelu estettiin 17 µg:n päivittäisellä D-vitamiinin saannilla, mutta tämän ei havaittu vaikuttavan radiuksen luuntiheyteen kuusi kuukautta kestävän tutkimuksen aikana. Yhteenvetona todetaan, että D-vitamiinin saanti on edelleenkin riittämätöntä tutkimusten kohderyhmillä. Tämä näkyy S-25-OHD- ja PTH-pitoisuuden sekä luunaineenvaihduntaa kuvaavien merkkiaineiden vuodenaikaisvaihteluna, mikä on haitallista luuston hyvinvoinnille. D-vitamiinin saantia tulisi lisätä, jotta vähintäänkin riittävä D-vitamiinitilanne (S-25-OHD>50 nmol/l) tai mahdollisesti jopa tavoiteltava D-vitaminitilanne (S-25-OHD≥80 nmol/l) saavutettaisiin. Jotta D-vitamiinin saannin lisääminen olisi kaikissa ikäryhmissä mahdollista, on suunniteltava nykyistä enemmän D-vitamiinilla täydennettyjä elintarvikkeita. Vitamin D is required for normal bone growth and maintenance of the skeleton throughout life. In Finland, like in many other Western countries, the population suffers from inadequate or deficient vitamin D status, especially during winter, which is thought to increase the risk of osteoporosis. New strategies to prevent osteoporosis are actively being sought. The main objective of this thesis was to determine whether vitamin D is feasible in the primary prevention of osteoporosis; does it affect bone mineral accrual during the growth period? A second goal was to ascertain whether seasonal variation in calcitropic hormones affects bone remodelling, and to elucidate the vitamin D intake needed to overcome this variation in different age groups. The subjects were healthy, free-living representatives of their respected age groups: 11- to 12-year-old girls (N=228), 21- to 49-year-old men (N=54) and 65- to 85-year-old women (N=52). Subjects participated in an intervention trial in which they were randomly assigned to a group receiving 0, 5, 10 or 20 µg of vitamin D as a supplement. All studies were performed double-blinded. Fasting blood and urine samples were collected together with data about, for instance, dietary intake of calcium and vitamin D and physical activity. In two studies bone mineral density (BMD) of subjects was measured at enrolment and at the end of the study. Laboratory analysis consisted of measurements of serum 25-hydroxyvitamin D (S-25-OHD), parathyroid hormone (S-PTH) and bone remodelling markers. Differences among months were observed in calcitropic hormones, bone formation marker, and BMD of the femur and vertebra in a cross-sectional study of early and mid pubertal girls, thus predicting seasonal variation. Vitamin D supplementation increased bone mineral accrual dose-dependently both in the femur and the vertebra of adolescent girls. Bone mineral accrual was 17.2% higher in the femur and 12.5% higher in the vertebra with 10 µg of vitamin D than with placebo, but the effect depended on compliance. The effect of vitamin D on bone was mediated through decreased resorption. Based on the results, a total intake of 15 µg/d appears to be sufficient for adolescent girls. The effect of vitamin D supplementation (5-20 µg/d) on S-25-OHD concentration of elderly women reached a plateau within six weeks. A concentration of 80 nmol/l, which is considered optimal, was not achieved with these dosages. We estimated that a concentration of 60 nmol/l, which is typically seen during summer in Finland, requires a total intake of 24 µg/d of vitamin D in elderly women. Seasonal variation in calcitropic hormones and bone resorption marker, but not in volumetric BMD of the radius or bone formation marker, was noted in healthy men in a prospective study. Vitamin D supplementation increased S-25-OHD, inhibited winter elevation of PTH and decreased bone formation marker, but did not affect BMD during this 6 month study. Adequate intake to avoid the season-related changes was calculated to be 17 µg/d. In summary, vitamin D intake remains inadequate among the target groups of this thesis, as reflected by seasonal variation in calcitropic hormones and bone metabolism. Dietary intake of vitamin D should be increased to achieve at least an adequate vitamin D status (S-25-OHD>50 nmol/l) and possibly an optimal vitamin D status (S-25-OHD>80 nmol/l) throughout the year. This could be accomplished by introducing new vitamin D-fortified foods to the market.
... Variation in the pattern and dynamics of skeletal growth complicate bone mass measurements in children and youth, and normative databases are insufficient [57, 58]. Techniques that are influenced by body size (eg, DXA) can be confounded by HIVassociated delays in growth596061 . Despite these caveats, almost all studies involving perinatally infected children have reported lower-than-expected bone mass62636465666768697071727374, as well as hormonal and calcium deficiencies [66, 68, 75, 76] . ...
Low bone mineral density (BMD) is prevalent in human immunodeficiency virus (HIV)-infected subjects. Initiation of antiretroviral
therapy is associated with a 2%–6% decrease in BMD over the first 2 years, a decrease that is similar in magnitude to that
sustained during the first 2 years of menopause. Recent studies have also described increased fracture rates in the HIV-infected
population. The causes of low BMD in individuals with HIV infection appear to be multifactorial and likely represent a complex
interaction between HIV infection, traditional osteoporosis risk factors, and antiretroviral-related factors. In this review,
we make the point that HIV infection should be considered as a risk factor for bone disease. We recommend screening patients
with fragility fractures, all HIV-infected post-menopausal women, and all HIV-infected men ⩾50 years of age. We also discuss
the importance of considering secondary causes of osteoporosis. Finally, we discuss treatment of the more severe cases of
bone disease, while outlining the caveats and gaps in our knowledge.
... Furthermore, if muscle was a causal factor during bone development, then increased muscle mass and muscle strength should precede the majority of bone mineral accrual. Although such a sequential relationship has been observed using two-dimensional dual-energy x-ray absorptiometry (32), recent three-dimensional computed tomographic (CT) data suggest that bone mineral accrual ceases before peak muscle strength is reached (43). At the other end of the spectrum, age-related sarcopenia presumably reduces muscle loading of bone and, therefore, should induce bone loss. ...
During locomotion and exercise, bone is subjected to forces induced by gravitational loading and muscle loading. The inherent link between these modes of loading has confounded emergence of either one as the principal anabolic or anticatabolic signal in bone. A paradigm has emerged in the literature stipulating that muscle loading is the larger of the two, and therefore, bone morphology is predominantly determined by muscle loads. In spite of the intuitive appeal of a muscle-bone unit tuned to the magnitude of contractile forces, little evidence exists for the relatively few, large-magnitude muscle contractions arising during daily activities to dominate the mechanosensory input of bone. Moreover, a review of the literature raises several inconsistencies in this paradigm and indicates that the alternative--gravitational loading--can have a significant role in determining bone mass and morphology. Certainly, the relative contribution of each type of loading will depend on the specific activity, the location of the bone within the skeleton, and whether the bone is weight-bearing or not. Most likely, a more comprehensive paradigm for explaining sensitivity of bone to loading will have to include not only large-magnitude gravitational and muscle loads, but also other factors such as high-frequency, low-magnitude signals generated by the muscles during postural adjustments.
... Wren et al. reported on the discrepancy in the timing of PBM when comparing DXA and QCT studies [82] ...
In this paper we discuss the bone densitometry systems available and their applicability in children and adolescents. Based on the knowledge that the majority of bone densitometry studies in children are performed using dual-energy X-ray absorptiometry (DXA), we focus attention on the sources of errors in interpretation of DXA studies in children and adolescents.
... Dual energy X-ray absorptiometry (DXA) is the most widely used tool for assessment of bone mass in the general population [7, 8]. However, DXA measures not only the mineral content of bone but also of the surrounding soft tissue [9, 10] limiting the interpretation of results [11]. CKD-5 patients represent a unique population particularly prone to developing soft tissue and vascular calcifications [12, 13]. ...
We evaluated the associations between dual energy X-ray absorptiometry (DXA) and histologically determined cancellous and cortical bone volume by controlling for vascular calcifications and demographic variables in hemodialysis (HD) patients. Femoral bone mineral density (f-BMD) was associated with cortical porosity.
Assessment of bone mass in chronic kidney disease patients is of clinical importance because of the association between low bone volume, fractures, and vascular calcifications. DXA is used for noninvasive assessment of bone mass whereby vertebral results reflect mainly cancellous bone and femoral results reflect mainly cortical bone. Bone histology allows direct measurements of cancellous and cortical bone volume. The present study evaluates the association between DXA and histologically determined cancellous and cortical bone volumes in HD patients.
In 38 HD patients, DXA was performed for assessment of bone mass, anterior iliac crest bone biopsies for bone volume, and multislice computed tomography for vascular calcifications.
While lumbar bone mineral density (l-BMD) by DXA was not associated with histologically measured cancellous bone volume, coronary Agatson score showed a borderline statistically significant association (P = 0.055). When controlled for age and dialysis duration, f-BMD by DXA was associated with cortical porosity determined by histology (P = 0.005).
The usefulness of l-BMD for predicting bone volume is limited most probably because of interference by soft tissue calcifications. In contrast, f-BMD shows significant association with cortical porosity.
... A significant limitation of almost all studies on peak bone density is that most have been conducted on white women only [2,[4][5][6][7]. This is a serious omission in the literature as racial differences in BMD have been demonstrated in a few studies [8][9][10]. ...
Racial/ethnic differences were observed in age at peak bone density and their correlates, with whites peaking at least 5 years earlier at the femoral neck than black and Hispanic women. Race-specific standards generated in this study could be useful when interpreting bone densitometry data in young women.
The influence of race/ethnicity on bone measurements has not been widely examined. This study identifies age and amount of bone accumulated at peak density and their correlates by race/ethnicity.
Bone mineral content (BMC) and bone mineral density (BMD) of the spine and femoral neck were measured by dual X-ray absorptiometry in 708 white, black, and Hispanic reproductive-aged women. Race-specific nonlinear models were used to describe the relationship between age and bone measurements, after adjusting for body weight and height. Log-transformed bone measurements were used to determine predictors based on multiple linear regression.
Predictors, which were race and site specific, included age, age at menarche, body weight, height, months of depot medroxyprogesterone acetate use, weight-bearing exercise, and alcohol use. Women of all races gained BMC and BMD at the spine up to 30-33 years of age. BMC and BMD of the femoral neck peaked among white women earlier (<or=16 years) than among blacks (BMC 22 years; BMD 21 years) and Hispanics (BMC 29 years; BMD 20 years).
Age at peak bone mass and its correlates differ by race/ethnicity. Race-specific standards generated in this study could be useful when interpreting bone densitometry data in young women.
... First, our data was generated by QCT and may not be applicable to the more commonly utilized application of DXA. Measurements from QCT were chosen for analysis in this study because QCT provides direct volumetric assessment of BMD which is believed to be important in BMD assessment in growing children [35][36][37] and because there is a relative dearth of information regarding the use of QCT in chronically ill children. Nonetheless, the selective nature of this sample may impart bias. ...
Skeletal bone accretion occurs throughout childhood. The integrity of this process can influence future adult bone health and the risk of osteoporosis. Although surveillance of children who are at risk of poor bone accretion is important, the most appropriate method to monitor childhood bone health has not been established. Previous investigators have proposed using bone age (BA) rather than chronological age (CA) when interpreting bone mineral density (BMD) values in children.
To investigate the value of BA assessment for BMD measurement in a cohort of children at risk of poor accretion.
A cohort of 163 children with brain tumors who completed both a BMD assessment (quantitative computed tomography, QCT) and who had a BA within a 6-month interval were identified. The difference in BMD Z-scores determined by CA and BA was determined. The impact of salient clinical features was assessed.
No significant difference between CA and BA Z-scores was detected in the overall cohort (P = 0.056). However, the scores in 18 children (all boys between the ages of 11 years and 15 years) were statistically determined to be outliers from the values in the rest of the cohort.
Interpretation of BMD with BA measurement might be appropriate and affect treatment decisions in peripubertal males.
... Human studies notwithstanding (4,7,68,99,100), animal models clearly illustrate the problematic nature of areal bone mineral density (aBMD), as assessed by DEXA during growth or adaptive alterations in bone geometry. This is partly because DEXA does not distinguish between changes in geometry and density (21, 68), nor cortical or cancellous bone, but also because its resolution is too low to detect small changes in bone dimensions that elicit substantial increases in bone strength (the holy grail of skeletal adaptation)(23). ...
Animal studies illustrate greater structural and material adaptations of growing bone to exercise than in adult bones but do not define effective training regimes to optimize bone strength in children. Controlled loading studies in turkey, rat, or mouse bones have revealed mechanisms of mechanotransduction and loading characteristics that optimize the modeling response to applied strains. Insights from these models reveal that static loads do not play a role in mechanotransduction and that bone formation is threshold driven and dependent on strain rate, amplitude, and partitioning of the load. That is, only a few cycles of loading are required at any time to elicit an adaptive response, and distributed bouts of loading, incorporating rest periods, are more osteogenic than single sessions of long duration. These parameters of loading have been translated into feasible public health interventions that exploit the insights gained from animal experiments to achieve adaptive responses in children and adolescents. Studies manipulating estrogen receptors (ER) in mice also demonstrate that skeletal sensitivity to loading during the peripubertal period is due to a direct regulation of mechanotransduction pathways by ER, and not just a simple enhancement of cell activity already marshaled by the hypothalamic-pituitary axis. Unfortunately, because the rate and timing of growth in small animals are completely different from those in humans, these models can be poor tools to elucidate periods during growth in youths, during which the skeleton is more sensitive to loading. However, there are insights from studies of human growth that can improve the interpretation of data from such studies of growth and development in animals.
Sex steroids are pivotal in skeletal development and maintenance throughout life. Testosterone primarily drives male cortical bone growth and periosteal expansion, particularly during puberty, while estradiol (E2) is essential for trabecular bone formation and inhibiting resorption. The conversion of testosterone to dihydrotestosterone and E2, the transport proteins, the somatotropic axis, and the nonandrogenic functions of the testis underscore the intricate interplay protecting male bone health.
Clinical models, including estrogen resistance, aromatase deficiency, and complete androgen insensitivity syndromes, highlight E2’s critical role in maintaining male bone integrity. The use of aromatase inhibitors and androgen deprivation therapy reveals the adverse effects of estrogen and androgen blockade, often resulting in substantial bone loss. Gender-affirming hormone therapies provide further insights into testosterone's influence on cortical bone during development and the maintenance role of sex steroids in adulthood.
This review digs into the link between male hypogonadism and osteoporosis, emphasizing testosterone replacement therapy (TRT) and findings from major trials, including T-Trial Bone, T4Bone, and TRAVERSE Fracture. While TRT has been shown to improve bone mineral density, its effect on fracture risk remains inconclusive. Unexpected findings from the TRAVERSE Fracture trial highlight the importance of caution and confirm that antiresorptive therapies remain the first-line treatment for male osteoporosis.
Investigating the synergistic effects of combining TRT with antiresorptive therapies, the effect of therapeutic timing on peak bone mass accrual, and the role of confounders in fracture risk are promising areas for future research to optimize male skeletal health.
Background:
The annotation of the regions of interest (ROI) of lumbar vertebrae by radiologists for bone density assessment is a tedious and time-intensive task. However, deep learning (DL) methods for image segmentation has the potential to substitute manual annotations which can significantly improve the efficiency of clinical diagnostics.
Objective:
The paper proposes a semi-supervised three-dimensional (3D) segmentation method for the ROI of lumbar vertebrae by integrating the tube masking masked autoencoder (MAE) pre-training.
Methods:
The paper proposes a method that modifies the masking strategy of the original MAE pre-training network. And the pre-training network is only trained by images without segmentation labels, when the training is finished, the weights will be saved for segmentation tasks. In downstream tasks, a semi-supervised approach utilizing pseudo-label generation is employed for training. This method leverages a small amount of labeled data to achieve the segmentation of ROI of the lumbar vertebrae.
Results:
The experimental results demonstrate that under the condition of limited annotated data, the proposed network improves the dice coefficient by 5–7% and reduces the hausdorff distance by 0.2∼0.6 mm compared to using the UNetr network alone for segmentation. When compared to the conventional MAE, the tube masking MAE presented in this paper assists effectively in segmentation, resulting in a 2% increase in the dice coefficient and a 0.24 mm reduction in the hausdorff distance.
Conclusion:
Automatic segmentation of the ROI of the lumbar vertebrae helps to shorten the time for doctors to annotate vertebrae during clinical bone density examinations. The paper employs the tube masking MAE pre-trained model to effectively extract contextual information of the 3D lumbar vertebrae, combining it with a semi-supervised network leveraging pseudo-label generation for fine-tuning, which leads to effective 3D segmentation of the lumbar vertebrae.
Background
The use of histogram analysis of computed tomography (CT) values is a potential method for differentiating between benign osteoblastic lesions (BOLs) and malignant osteoblastic lesions (MOLs).
Purpose
To explore the diagnostic efficacy of histogram analysis in accurately distinguishing between BOLs and MOLs based on CT values.
Material and Methods
A total of 25 BOLs and 25 MOLs, which were confirmed through pathology or imaging follow-up, were included in this study. FireVoxel software was used to process the lesions and obtain various histogram parameters, including mean value, standard deviation, variance, coefficient of variation, skewness, kurtosis, entropy value, and percentiles ranging from 1st to 99th. Statistical tests, such as two independent-sample t-tests and the Mann–Whitney U test with Bonferroni correction, were employed to compare the differences in histogram parameters between BOLs and MOLs. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficacy of each parameter.
Results
Significant differences were observed in several histogram parameters between BOLs and MOLs, including the mean value, coefficient of variation, skewness, and various percentiles. Notably, the 25th percentile demonstrated the highest diagnostic efficacy, as indicated by the largest area under the curve in the ROC curve analysis.
Conclusion
Histogram analysis of CT values provides valuable diagnostic information for accurately differentiating between BOLs and MOLs. Among the different parameters, the 25th percentile parameter proves to be the most effective in this discrimination process.
Peak bone mass (PBM) is an important determinant of osteoporotic fracture risk later in life. Bone mineral mass accumulation from infancy to postpuberty is a complex process implicating interactions of genetic, endocrine, mechanical, and nutritional factors. PBM is attained in the axial skeleton and in the proximal femur by the end of the second decade of life. The increase in mass and strength is essentially due to an increment in bone size, with volumetric bone mineral density (BMD) changing very little during growth. In adult women, an increase of PBM by 10%, that is, by approximately 1 standard deviation (SD), could decrease the risk of fragility fracture by 50% or be equivalent to retarding menopause by 14 years. Bone mineral mass during growth follows a trajectory. The main influencing factor is genetics. Increasing calcium intake or mechanical loading can shift upward the age-bone mass trajectory, while chronic diseases and their treatment can shift it downward. Prepuberty appears to be an opportune time for obtaining a substantial benefit of increasing physical activity with appropriate intakes of calcium and proteins.
Recent observations indicate that the cross-sectional area (CSA) of vertebral bodies are on average 10% smaller in healthy newborn girls than in newborn boys - a striking difference that increases during infancy and puberty, and is greatest by the time of sexual and skeletal maturity. The smaller vertebral CSA in females is associated with greater spinal flexibility, and could represent the human adaptation to fetal load in bipedal posture. Unfortunately, it also imparts a mechanical disadvantage that increases stress within the vertebrae for all physical activities. This review summarizes the potential endocrine, genetic, and environmental determinants of vertebral cross-sectional growth and current knowledge on the association between the small female vertebrae and increased risk for a broad array of spinal conditions across the lifespan.
Objectives: We aimed to establish the typical rate of skeletal mineralisation in the growing sheep. The sheep (size, ease of handling, cost and bone physiology) is establishing itself as an appropriate model for bone research.
Materials and Methods: Body composition including bone density at 4 time points in the first two years was performed using DXA on a cohort of 14 developing lambs, as well as measurements in comparable adult sheep.
Results: Adult levels of bone density are reached by 18 months and lean body mass by 2 years in sheep.
Conclusions: Depending on the indications for studying bone and other metabolism in sheep, the rate of development should be considered in selecting the age group of experimental animals.
Keywords :
Bone densitometry; sheep; growth; normal range; dual energy X-ray absorptiometry.
Peak bone mass (PBM) corresponds to the amount of bony tissue present at the end of skeletal maturation. It is a major determinant
of the risk of fractures later in life, because there is an inverse relationship between fracture risk and areal bone mineral
density, in women as well as in men. From epidemiological studies it can be assumed that an increase of 10% of PBM in the
female population, corresponding to approximately 1 standard deviation, would be associated with a 50% decrease in the risk
of fracture. Hence, exploring ways of increasing PBM could be considered as a valuable measure in the primary prevention of
osteoporosis. Bone mineral accumulation from infancy to postpuberty is a complex process. It can be appreciated with the availability
of noninvasive techniques able to accurately measure areal (a) or volumetric (v) bone mineral density (BMD) at several sites
of the skeleton by either dual X-ray absorptiometry (DXA) or quantitative computed tomography (QCT). Noninvasive specific
evaluations of the cancellous and cortical bone compartments, even of trabecular microstructure, are also becoming available
(see Chapter 3). These techniques allow one to capture part of the change in the macroarchitecture or geometry of the bones which along
with the mineral mass strongly influence the resistance to the mechanical strain. This chapter attempts to summarize some
of the knowledge that has accumulated over the past few years on the characteristics of normal bone mass development from
infancy to the end of the skeleton maturation and the genetic and environmental factors influencing bone mass accrual, hence
PBM.
During locomotion and exercise, bone is subjected to forces induced by gravitational loading and muscle loading. The inherent link between these modes of loading has confounded emergence of either one as the principal anabolic or anticatabolic signal in bone. A paradigm has emerged in the literature stipulating that muscle loading is the larger of the two, and therefore, bone morphology is predominantly determined by muscle loads. In spite of the intuitive appeal of a muscle–bone unit tuned to the magnitude of contractile forces, little evidence exists for the relatively few, large-magnitude muscle contractions arising during daily activities to dominate the mechanosensory input of bone. Moreover, a review of the literature raises several inconsistencies in this paradigm and indicates that the alternative—gravitational loading—can have a significant role in determining bone mass and morphology. Certainly, the relative contribution of each type of loading will depend on the specific activity, the location of the bone within the skeleton, and whether the bone is weight-bearing or not. Most likely, a more comprehensive paradigm for explaining sensitivity of bone to loading will have to include not only large-magnitude gravitational and muscle loads, but also other factors such as high-frequency, low-magnitude signals generated by the muscles during postural adjustments.
Bone mass and architecture are primarily of importance in relation to load-bearing. Despite this it is common to ascribe the role of “regulator of bone mass” to practically any substance that influences bone cell activity. Here we argue that “regulation” of bone mass and architecture, as a process to achieve particular local structural objectives, should be distinguished from “influence” arising from effects on (re)modeling derived from local, systemic or centrally-derived factors that are uninfluenced (often uninfluencible) by the architectural outcome. The mechanisms involved in structural regulation of bone mass and architecture in relation to functional loading are commonly termed the “mechanostat.” Its controlling input is assumed to be the mechanical strains engendered within the tissue by customary loading. Even in its initial stages during which strains are transduced into biochemical responses the mechanostat does not appear to employ a unique signaling pathway; instead it shares a number of pathways used by local or systemic influences that have no feedback directly related to any particular bone mass or architecture. Through the effect of these interactions the initial assessment of strain, as well as the early responses to it, are sensitive to context. The effect of different contexts such as high or low estrogen or PTH can diminish, complement or synergize with the consequences of strain-related stimulation. At extreme levels the effect of context may mask the consequences of strain completely. Strategies for therapeutic intervention to achieve structurally beneficial effects on bone (re)modeling should therefore be designed to synergize, rather than to compete, with the mechanisms of the mechanostat.
Peak bone mass is an important factor in the lifetime risk of developing osteoporosis. Large, longitudinal studies investigating the age of attainment of site-specific peak bone mass are lacking. OBJECTIVE AND MAIN OUTCOME MEASURES: The main outcome measures were to determine the site-specific development of peak bone mass in appendicular and axial skeletal sites and in the trabecular and cortical bone compartments, using both dual x-ray absorptiometry and peripheral computed tomography.
In total, 833 men [aged 24.1 ± 0.6 yr (mean ± sd)] from the original population-based Gothenburg Osteoporosis and Obesity Determinants Study (n = 1068) were included in this follow-up examination at 61.2 ± 2.3 months. Areal bone mineral density (aBMD) was measured with dual x-ray absorptiometry, whereas cortical and trabecular volumetric bone mineral density and bone size were measured by peripheral computed tomography at baseline and at the 5-yr follow-up.
During the 5-yr study period, aBMD of the total body, lumbar spine, and radius increased by 3.4, 4.2, and 7.8%, respectively, whereas a decrease in aBMD of the total hip of 1.9% was observed (P < 0.0001). Increments of 2.1 and 0.7% were seen for cortical volumetric bone mineral density of the radius and tibia, respectively (P < 0.0001), whereas cortical thickness increased by 3.8% at the radius and 6.5% at the tibia due to diminished endosteal circumference (radius 2.3% and tibia 4.6%, P < 0.0001).
aBMD decreased at the hip but increased at the spine and radius, in which the increment was explained by continued mineralization and augmented cortical thickness due to endosteal contraction in men between ages 19 and 24 yr.
Using computed tomography (CT), we found the decreases in bone size of vertebrae and femur, cortical bone area (CBA) of femur and bone density (BD) of vertebrae in prepubertal female with Turner syndrome (TS) compared to those of controls.
Bone mineral density results from previous studies utilizing single-photon absorptiometry (SPA) or dual-energy X-ray absorptiometry (DXA) in children with TS are controversial. The present study used CT to assess the differences in cancellous and cortical bone size and BD between prepubertal TS patients prior to growth hormone therapy and historical age and ethnicity-matched female controls.
Anthropometrics and CT bone measurements including cross-sectional area (CSA) and BD of lumbar vertebrae and femur and CBA of femur in prepubertal TS females were reviewed and compared with those in controls.
Twenty-two prepubertal TS patients had delayed bone age, were shorter and lighter than controls (Ps < 0.001). After adjusting for weight, height and skeletal age, vertebral BD and CBA of the femur were lower in patients than in controls (P < 0.001 and P = 0.021, respectively). However, after additional adjusting for puberty, results were not different from controls. While a positive correlation between vertebral BD and age was noted in controls (r = 0.367, P = 0.092), a significant negative correlation was noted in patients (r = -0.615, P = 0.002).
While the decrease in vertebrae and femur sizes of patients with TS appeared to be secondary to their small body size, the decreased BD of vertebrae and CBA of femur were likely secondary to estrogen deficiency.
Although vitamin D and bone metabolism are closely related, few studies have addressed the effects of vitamin D status on bone in men at time of peak bone mass. The objectives of this study were to evaluate the prevalence of vitamin D inadequacy in a cross-sectional study in young men and the effects of vitamin D and parathyroid hormone (PTH) on bone mass, bone markers and metabolic function.
The study population consisted of 783 men aged 20-29 years.
Bone mineral density (BMD) of the total hip, femoral neck and lumbar spine was measured. dual-energy X-ray absorptiometry was used to evaluate total body fat mass (BFAT). Visceral fat mass and abdominal subcutaneous fat mass (ViFM and ScFM) were assessed using magnetic resonance imaging. A radioimmunoassay was used to measure the level of 25-hydroxy vitamin D (25OHD).
The prevalence of vitamin deficiency (serum 25OHD < 50 nm) was 6·3% during summer and 43·6% during winter. Serum 25OHD was associated with BMD at all sites and inversely associated with bone-specific alkaline phosphatase and directly with carboxyterminal telopeptide of type-1-collagen. 25OHD and PTH were inversely associated with BFAT, whereas 25OHD also was inversely associated with body mass index, waist-hip ratio, ViFM and ScFM after adjustment for confounders. The associations were found only to be present in participants with insufficient levels of 25OHD. 25-Hydroxy vitamin D and PTH were inversely related to insulin resistance in vitamin-insufficient participants only. No associations between PTH or 25OHD and blood pressure were noted.
The study showed a high prevalence of 25OHD deficiency in young, northern European men, which was significantly associated with decreased BMD. PTH and 25OHD were found to be inversely related to the markers of insulin resistance.
Because DXA is a projection technique, anterior-posterior (AP) measurements of the spine include the posterior elements and the vertebral body. This may be a disadvantage because the posterior elements likely contribute little to vertebral fracture resistance. This study used QCT to quantify the impact of the posterior elements in DXA AP spine measures. We examined 574 subjects (294 females and 280 males), age 6-25 yr, with DXA and QCT. QCT measures were calculated for the cancellous bone region and for the vertebral body including and excluding the posterior elements. DXA data were analyzed for the entire L(3) vertebra and for a 10-mm slice corresponding to the QCT scan region. BMC and BMD were determined and compared using Pearson's correlation. The posterior elements accounted for 51.4 +/- 4.2% of the total BMC, with a significant difference between males (49.9 +/- 4.0%) and females (52.8 +/- 3.9%, p < 0.001). This percentage increased with age in younger subjects of both sexes (p < 0.001) but was relatively consistent after age 17 for males and 16 for females (p > 0.10). DXA areal BMD and QCT volumetric BMD correlated strongly for the whole vertebra including the posterior elements (R = 0.83), with BMC measures showing a stronger relationship (R = 0.93). Relationships were weaker when excluding the posterior elements. We conclude that DXA BMC provides a measure of bone that is most consistent with QCT and that the contribution of the posterior elements is consistent in young subjects after sexual maturity.
Adolescence is a critical period for determining peak bone mass. During this time, bone formation prevails over resorption, and approximately 40% of the total bone mass is accumulated. Several factors affect the accretion of bone mass during adolescence. Although genetic predisposition, age, race, and ethnicity cannot be modified, factors such as nutrition, physical activity, and lifestyle choices can be changed. Promoting a healthy lifestyle, regular weight-bearing physical activity, and a healthy diet with optimal calcium and vitamin D intake may prove to be the best way to achieve a maximal peak bone mass. This review discusses the known, the unknown, and the controversial regarding bone metabolism during adolescence.
As children grow, they accumulate bone mineral, which serves as a "bone bank" for the future. Any condition that interferes with normal bone mineral accrual during childhood has the potential to reduce peak bone mass and subsequently increase future risk for fracture. In contrast to adults, for whom dual-energy x-ray absorptiometry (DXA) has become the standard clinical instrument for assessing bone mineral density and criteria have been developed to define osteopenia and osteoporosis, information for children is still limited. Numerous issues confound the interpretation of DXA-derived bone mineral density measurements in children, and clinicians often find themselves caught between the limitations of these methods and the practical issue of taking care of their pediatric patient. The explosion of treatment options for postmenopausal osteoporosis has resulted in new options for the treatment of children and adolescents. However, most of these agents have not been sufficiently well studied in children to permit the development of standardized treatment guidelines.
To determine when spinal bone density reaches its peak, the trabecular vertebral density was assessed, via quantitative computed tomography, among females from two age groups: (1) adolescents (aged 14-19 years; N = 24); and (2) young adults (aged 25-35 years; n =24). The adolescent girls had a higher mean trabecular vertebral density (P less than 0.01), suggesting that spinal density reaches its peak around the time of cessation of longitudinal growth and epiphyseal closure.
We made longitudinal measurements of bone mineral density (BMD) in 139 normal women (ages 20-88 yr) at midradius (99% cortical bone) and lumbar spine (approximately 70% trabecular bone) by single- and dual-photon absorptiometry. BMD was measured 2-6 (median, 3) times over an interval of 0.8-3.4 yr (median, 2.1 yr). For midradius, BMD did not change (+0.48%/yr, NS) before menopause but decreased (-1.01%/yr, P less than 0.001) after menopause. For lumbar spine, there was significant bone loss both before (-1.32%/yr, P less than 0.001) and after (-0.97%/yr, P = 0.006) menopause; these rates did not differ significantly from each other. Our data show that before menopause little, if any, bone is lost from the appendicular skeleton but substantial amounts are lost from the axial skeleton. Thus, factors in addition to estrogen deficiency must contribute to pathogenesis of involutional osteoporosis in women because about half of overall vertebral bone loss occurs premenopausally.
A previous study showed that measurements of total-body bone mineral changes made with a Hologic QDR 1000W were unreliable when the subjects underwent weight change. The study has been extended to dual energy X-ray absorptiometry (DXA) apparatus from other manufacturers. Re-analysis of published results during weight loss using a Lunar DPX showed that they varied with the software used. Using the Extended mode, there was a 1% loss of bone mineral areal density (BMD), but no significant change in bone mineral content (BMC) or bone area (BA) following a weight loss of 16 kg, whereas the use of the Standard mode led to a larger fall of BMC and BMD. Similar findings arose from the consideration of two studies using Norland XR 26 HS absorptiometers. On the other hand, separation of two groups with similar weight changes from the population studied with a Hologic QDR 1000W confirmed that BMC changed directly with weight, but there was an inverse relationship for BMD, owing to an inappropriate change of BA. The use of Hologic Enhanced and Standard software modes led to significant differences in initial readings and measured changes. With each instrument there was a strong correlation between changes in BA and changes in BMC. When 6 kg of lard was wrapped around the limbs of volunteers or a semi-anthropomorphic phantom to simulate weight change, there were spurious increases of measured BMC and BA by about 5% with each instrument. There were no changes of BMD with Lunar, variable results with Norland, but decreases with Hologic. The results observed in vivo could be explained by the effects of fat changes, without there being any real change of bone mineral. Changes of BMD in the skeleton of the phantom were underestimated with all three brands. The anomaly observed with the Hologic QDR 1000W is less apparent with a Lunar DPX or a Norland XR 26, but there are sufficient uncertainties for all total-body measurements during weight change to be treated with suspicion.
A study of the compressive failure strength and mineral content of cancellous bone was performed. The matrial was obtained from 150 selected autopsies. Exclusion of thirteen of the selected cadavera on clinical or histological grounds left 137 cadavera for review: seventy-two male and sixty-five female. Cubes of cancellousbone from the third lumbar vertebral body and from the calcaneal tuberosity were obtained in a standard way and subjected to compressive loading and ash-weight determination. The findings justified the following conclusions:
1. Compressive failure strength is a reliable function of the mineral content of cancellous bone in the vertebra or the calcaneus. This relationship is maintained irrespective of age or sex.
2. In an autopsy population in which every effort was made to select normal individuals there is a definite and progressive trend toward decreasing bone strength and mineral content with advancing age.
3. There is ho significant difference between the strength or mineral content of cancellous bone of male and female cadavera below the age of fifty. Over the age of fifty the strength and mineral content is significantly lower in female cadavera.
4. The decrease in bone mineral and strength appears to develop earlier in the vertebra than in the calcaneus.
5. It is suspected that changes which parallel those observed in female cadavera would be seen in male cadavera as well if the population sampled included a larger number of individuals over the age of eighty.
6. The relationship between calcaneal mineral content and compressive stregth and the same determinations in the vertebra is only fair. The fact that the correlation is particularly low in males and in the younger group suggests that activity may influence cancellous bone strengh and mineral content. Evidence is offered to show that this influence is exerted by way of the distribution and orientation of trabeculae.
7. The effect of generalized osteoporosis on the calcaneus is delayed and appears to be influenced by activity. It would seem that the calcaneus is an unsatisfactory bone for following the dynamics of a generalized demineralizing process.
This chapter discusses the pediatric use of dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), peripheral QCT (pQCT), quantitative ultra- sound (QUS), magnetic resonance imaging (MRI), and X-ray radiogrammetry for bone mass measurement. These techniques can be compared using several criteria, including speed of measurement, radiation exposure, cost, and regions of the skeleton that can be scanned. These techniques also vary in accuracy (the difference between bone measurement and ash weight) and precision (the reproducibility of repeated measurements). For clinical purposes, precision is of greater importance than accuracy. QCT and MRI can distinguish trabecular from cortical bone, whereas DXA provides only a composite measurement of both compartments. There are differences in the availability of normative pediatric data to be used as reference values when interpreting scans performed for clinical purposes. The recognition of importance of early bone health has increased the demand for bone mineral assessments in children and adolescents. For clinicians, densitometry is important for screening the bone health of young patients with myriad chronic diseases associated with low bone mass and fractures early in life. The goal of mass assessments in this setting is to identify patients with skeletal fragility and to monitor response to therapy.
Address correspondence to Owe Löfman, Centre for Public Health Sciences, University Hospital, S-581 85 Linköping, Sweden
Lateral spine dual-energy x-ray absorptiometry (DXA) selectively measures the trabecular-rich vertebral bodies without the contributions of the cortical-rich posterior elements of the spine and is less affected by spinal degenerative disease than posterior-anterior DXA. We tested whether lateral DXA detects vertebral osteoporosis more often and is more sensitive to age-related bone loss than posterior-anterior DXA in 193 healthy, community-dwelling men aged 51–81 years (mean ± SD; 67 ± 8 years). All men had supine lateral, posterior-anterior, and proximal femur DXA scans on a Hologic QDR 2000 densitometer. A subset (n = 102) had repeat scans after 4 years to determine annualized rates of change in bone mineral density (BMD). Age was inversely and significantly associated with BMD in the midlateral (r = −0.27) and lateral (r = −0.24) but not posterior-anterior (r = 0.04) projections. Midlateral (−1.43 ± 3.48% per year; p = 0.0001), lateral (−0.27 ± 1.68% per year; p = 0.12), and hip (−0.19 ± 1.02% per year; p = 0.06) BMD decreased, whereas posterior-anterior BMD increased (0.73 ± 1.11% per year; p = 0.0001) during follow-up. When compared with normal values in 43 men aged 21–42 years, mean T scores were significantly lower with lateral (−1.47 ± 1.32) and midlateral (−1.57 ± 1.36) than posterior-anterior (−0.12 ± 1.30; p < 0.0001) DXA. Only 2.6% of the older men were considered osteoporotic (T score ≤ −2.5) at the posterior-anterior spine, whereas 11.0% were osteoporotic at the femoral neck, 22.5% at the lateral spine, and 24.6% were osteoporotic at the midlateral spine. We conclude that supine lateral DXA identifies considerably more men as osteoporotic and is more sensitive to age-related bone loss than posterior-anterior DXA. Spinal osteoporosis may represent a substantially greater health problem among older men than previously recognized.
To test whether bone mass increases in healthy nonpregnant white women during early adult life after cessation of linear growth; and to test whether various self-chosen levels of physical activity and nutrient intake or use of oral contraceptives influences this increase in bone mass.
Longitudinal prospective study of up to 5 years of 156 healthy college-aged women full-time students attending professional schools in universities in the Omaha, Neb, area.
University medical center.
A convenience sample of healthy women students from Omaha-area professional schools. Any candidate with an illness, condition, or medication (except oral contraceptives) thought to affect general health or bone mass was excluded.
None.
Clinical and family histories of disease, particularly osteoporosis; oral contraceptive use; bone mineral densities of the spine, forearm, and total body by dual- and single-photon absorptiometry; estimates of nutrient intake by repeated 7-day diet diaries; and measures of physical activity using a physical activity monitor.
The median gain in bone mass for the third decade of life, expressed as a percentage per decade, was 4.8% for the forearm, 5.9% for lumbar bone mineral content, 6.8% for lumbar bone mineral density, and 12.5% for total body bone mass (P < .0001 in all cases). By both bivariate and multiple regression analysis the rate of gain in bone density of the spine was negatively correlated with age and positively correlated with calcium/protein intake ratio and physical activity (multiple r = .31; P = .004). Bivariate analysis showed that use of oral contraceptives was associated with greater gain in total body bone mass (r = .31, P = .01). The estimated age when mineral acquisition ceased ranged from 28.3 years to 29.5 years at the several study sites.
Gain in bone mass occurs in healthy young women during the third decade of life. Physical activity and dietary calcium intake both exert a positive effect on this bone gain. Use of oral contraceptives exerts a further independent positive effect. Changes in life-style among college-aged women, involving relatively modest increases in physical activity and calcium intake, may significantly reduce the risk of osteoporosis late in life.
A high degree of uncertainty and irritation predominates in the assessment and comparison of radiation dose values resulting from measurements of bone mineral density of the lumbar spine by photon absorptiometry and X-ray computed tomography. The skin dose values which are usually given in the literature are of limited relevance because the size of the irradiated volumes, the relative sensitivity of the affected organs and the radiation energies are not taken into account. The concept of effective dose, sometimes called whole-body equivalent dose, has to be applied. A detailed analysis results in an effective dose value of about 1 microSv for absorptiometry and about 30 microSv for computed tomography when low kV and mAs values are used. Lateral localizer radiographs, which are necessary for slice selection in CT, mean an additional dose of 30 microSv. Lateral X-ray films of the spine which are frequently taken in combination with absorptiometry result in a dose of 700 microSv or more. The concept of effective dose, the basic data and assumptions used in its assessment and a comparison with other dose burdens (for example the natural background radiation, of typically 2400 microSv per year) are discussed in detail.
The bone mineral density (BMD) of the lumbar spine and proximal femur was measured using dual-energy X-ray absorptiometry in 717 healthy women aged 20-70 years. The maximal mean BMD was found at the age of 35-39 years in the spine and at the age of 20-24 in the femoral neck and Ward's triangle. No significant change in lumbar BMD was found from the age of 20 to 39 years. The spinal BMD values were relatively stable from age 20 to 39 years, whereas a linear decrease in BMD in the femoral neck and Ward's triangle was already apparent in the youngest age group (20-24 years). The major fall in BMD in all sites was related to the menopause. The overall decreases in BMD from the peak values to those at age 65-70 years were 20.4%, 19.0% and 32.6% in the lumbar spine, femoral neck and Ward's triangle, respectively. The correlation of trochanteric BMD with age was poor. BMD was positively correlated with weight in all measurement sites. Nulliparity was found to be a risk factor for osteoporosis. The present study confirmed that the menopause has a significant effect not only on spinal BMD but also on femoral BMD. Lumbar BMD was lower and BMDs in the proximal femur were higher in Finnish women than in white American women. This emphasizes the importance of national reference values for BMD measurements.
A cross-sectional study of 351 healthy Finnish women aged 20-76 years was done to establish reference values of bone mineral density (BMD) using dual-energy X-ray absorptiometry (DEXA). The effects of age and of several physical and lifestyle factors on BMD of the lumbar spine and proximal femur (femoral neck, trochanter, and Ward's triangle area) were investigated. Altogether 58 women were excluded from the final analysis due to significant spinal osteoarthritis or other diseases or drugs known to influence calcium or bone metabolism. The precision of the method was 0.9, 1.2, 2.7, and 2.4% in the lumbar, femoral neck, Ward's triangle and trochanter area, respectively. Lumbar BMD was increased by 30% (P less than 0.001) in 15 patients with osteoarthritis (21% of women 50 years or older), but it was apparently unaffected in 5 cases with aortic calcification. Except for the trochanter area, BMD diminished along with age, and this was significant after the menopause. The peak of mean BMD was observed at the age of 31-35 years in the spine and at the age of 20-25 years in the femoral neck and Ward's triangle. BMD was in a positive relationship to weight both in premenopausal and postmenopausal women and to the use of oral contraceptives in premenopausal women and to that of estrogen replacement therapy in postmenopausal women. Labors and pregnancies had a weak positive effect on BMD in premenopausal women. As compared with nonusers premenopausal women who had used alcohol showed a slightly decreased BMD of Ward's triangle. In postmenopausal women there was a positive correlation between alcohol intake and BMD.
Two hundred and twenty-five premenopausal women were studied to evaluate age-related changes in trabecular bone mass. Measurements were made at the lumbar spine and femoral neck by dual photon absorptiometry. It was found that spinal bone density increased significantly from the 20s to reach a peak in the mid-30s. Identical trends were observed in total bone mass and bone mass normalized by length. Bone loss then proceeded at a rate of 1% per year, and by the early 50s, 10% of peak spinal density was lost. There was no peak in femoral neck density; loss commenced in the late 20s and continued at a rate of 0.4% per year. The cumulative premenopausal loss from the femur at 9% was comparable to that in the spine. It is concluded that significant amounts of trabecular bone are lost from both the spine and femoral neck before the menopause. The implications of these findings for the prevention of osteoporosis are discussed.
In order to investigate the influence of fat on bone in dual-energy absorptiometry measurements, we evaluated a special phantom on the three scanners: Lunar DP3, Lunar DPX and Hologic QDR-1000. The phantom employed hydroxyapatite blocks of various thicknesses to simulate bone, water to simulate muscle and lucite to simulate fat. The lucite plates were arranged in one and two layers in three different configurations: over the whole measurement area, over the hydroxyapatite blocks only and at both sides of the hydroxyapatite blocks. For all scanners, no influence of fat could be demonstrated if it was homogeneously distributed over the whole measurement area. However, changes in area bone-density were observed if fat was distributed inhomogeneously over the measurement area. Fat over only the bone area reduced the measured bone values by 0.051 g/cm2 per cm fat layer. Fat over only the soft-tissue area increased the measured bone values by the same amount. These results apply to the Lunar DPX scanner. The results for the Lunar DP-3 scanner are similar; those for the Hologic QDR-1000 show a slightly smaller fat dependence of 0.044 g/cm2 per cm fat layer. The fat influences are not dependent on the amount of bone and only minimally on the soft-tissue thickness. A change of 50% in the fat content of the bone marrow will change the measured area bone-density of an averaged sized vertebra by 5-6% depending on scanner model. Inhomogeneous fat distribution in soft tissue, resulting in a difference of 2 cm fat layer between soft-tissue area and bone area, will influence the measured area bone-density by 9-10%.
Bone mineral density (BMD) of the spine (n = 892) and femur (n = 634) was measured using dual-photon absorptiometry in normal white women from seven diverse locations. The same model commercial scanner with a 153Gd source was used in all locations (SD = 1.3% among locations). There was not an age-associated decrease of spinal BMD during young adulthood (20-40 years); the correlation of age and femoral BMD in this period was low but significant (r = -0.21). There was a narrow range of intra-population variation at all ages (10-12%). The cross-sectional data showed an average diminution of about 20% in the spine and 25% in the femur between 40 and 70 years of age, followed by a continued but slower, decrease of density in older women. Adjustment of values for height and weight was called for mainly at extremes of body size.
Vertebral and peripheral bone mass have been measured with single and dual photon absorptiometry and radiogrammetry in 146 male and 220 female volunteers ranging in age from 20 to 85 yr. One hundred four subjects with interfering diseases, treatment, or x-ray manifestations of lumbar osteoarthritis were excluded for purposes of this study. Patterns of age-related bone gain and diminution differed between sexes and measuring sites. The effect of menopause on the peripheral and vertebral skeleton also differed. Men, at all measured sites, have more bone than women. In the fifth decade, however, women's lumbar bone mineral content was almost equal to the value found in men. Bone loss associated with aging was more marked in women than in men and started, for the lumbar spine, at about the age of 25 yr in both women and men and, for the peripheral bones, at the age of 55 in women and 65 in men. Bone loss in the spine in women was not linear. Women in the fifth and sixth decade, who still had menstruation, differed significantly from those who had not menstruated for at least the last 6 mo. Bone diminution at menopause was twice as great in the lumbar spine than elsewhere in the peripheral skeleton, 15% versus 7%. Of the 25% total bone loss of the spine during adult life in women, 60% was lost within 10 yr after menopause. Estrogen deficiency, not aging, is the predominant cause of bone loss in the spine. For the peripheral skeleton, there is a two-component decrease, a rapid loss induced by the menopause superimposed on a slower age-related loss. Although there was a significant correlation between peripheral and vertebral bone mass indices, it was clear that observations made at one site will not necessarily reflect changes observed at another site.
We measured the trabecular bone volume (TBV) of 62 iliac crest biopsies taken from women admitted to lymphoma protocols at Stanford University between 1970-1981. All subjects were active, cycling premenopausal women, with bone marrows that were negative for tumor. Disease status was stage III or less in 90% of the subjects. Trabecular bone volume was negatively correlated with age, and the annual predicted loss of bone was 0.14-0.18% TBV, or 0.7% of the original bone volume. In addition, there was a substantial range of normal TBV at any given age, evident even during adolescence. This study demonstrates that TBV is lost from iliac crest throughout adult life. The large spread in TBV indicates further that factors operating during adolescence or even earlier may have an important impact on skeletal mass.
1. Bone mineral content of the second, third and fourth lumbar vertebrae was determined in normal women and women with clinical osteoporosis by using dual-photon (153Gd) absorptiometry.
2. A cross-sectional study of 70 normal women (aged 19–88 years) showed a bone loss of 44% from the age of around 34 years throughout life.
3. Longitudinal data from 59 normal women confirmed that the vertebral bone loss started before the menopause. An accelerated bone loss amounting to nearly 6% per year was seen immediately after the menopause. The bone loss of older women was slower.
4. Mean lumbar bone mineral content of 36 women (aged 48–93 years) with recent fractures of their femoral neck after minor trauma equalled that of age-matched normal women. Lumbar bone mineral content of the women with intratrochanteric femoral neck fractures was lower than that of the women with medial femoral neck fractures.
5. Mean lumbar bone mineral content of 72 women (aged 58–89 years) with primary osteoporosis was 41% lower than that of normal premenopausal women and 18% lower than that of age-matched controls. A weak inverse relationship between lumbar bone mineral content and the number of compression fractures was found. A weak inverse relationship between lumbar bone mineral content and the number of compression fractures was found.
6. Women with lumbar bone mineral content values below the 95% confidence limits for normal premenopausal women are at risk of future vertebral compression fractures, the fracture risk being inversely related to lumbar bone mineral content.
The so-called peak bone mass (PBM) represents the highest amount of bony tissue achieved during life at a given site of the skeleton. It has been suggested that PBM might be achieved as late as the fourth decade, but recent data have indicated that PBM is already achieved by the end of sexual maturation, namely at the end of the second decade. The solving of this apparent controversy is of interest for a better understanding of bone homeostasis and for defining the cohort of normal subjects to be evaluated in order to establish a PBM reference range--necessary for the diagnosis of osteoporosis and evaluation of the fracture risk. To study bone mass evolution in young healthy adults and to determine whether such a cohort can be used to establish PBM reference values, we measured bone mineral density (BMD) in sixty 20- to 35-year-old young healthy adults by dual-energy X-ray absorptiometry at the levels of the lumbar spine (in both anteroposterior and lateral views), femoral neck, trochanter region, total hip and of Ward's triangle, as well as whole-body BMD and bone mineral content (BMC) in cross-sectional and longitudinal studies. In the cross-sectional analysis, none of the bone mass variables was dependent on age using linear regression analysis. The longitudinal study indicated that the mean changes in lumbar spine, proximal femur and whole body BMD or BMC determined after a 1-year interval were not statistically different from zero in either females or males aged 20-35 years.(ABSTRACT TRUNCATED AT 250 WORDS)
Peak bone mass, which can be defined as the amount of bony tissue present at the end of the skeletal maturation, is an important determinant of osteoporotic fracture risk. Measurement of bone mass development. The bone mass of a given part of the skeleton is directly dependent upon both its volume or size and the density of the mineralized tissue contained within the periosteal envelope. The techniques of single-1 and dural-energy photon or X-ray absorptiometry measure the so-called 'areal' or 'surface' bone mineral density (BMD), a variable which has been shown to be directly related to bone strength. Bone mass gain during puberty. During puberty the gender difference in bone mass becomes expressed. This difference appears to be essentially due to a more prolonged bone maturation period in males than in females, with a larger increase in bone size and cortical thickness. Puberty affects bone size much more than the volumetric mineral density. There is no significant sex difference in the volumetric trabecular density at the end of pubertal maturation. During puberty, the accumulation rate in areal BMD at both the lumbar spine and femoral neck levels increases to four- to sixfold over a 3- and 4-year period in females and males, respectively. Change in bone mass accumulation rate is less marked in long bone diaphyses. There is an asynchrony between the gain in statural height and bone mass growth. This phenomenon may be responsible for the occurrence of a transient period of a relative increase in bone fragility that may account for the pattern of fracture incidence during adolescence.(ABSTRACT TRUNCATED AT 250 WORDS)
To determine the timing of peak bone mass and density, we conducted a cross-sectional study of bone mass measurements in 265 premenopausal Caucasian females, aged 8-50 yr. Bone mass and bone mineral density were measured using dual X-ray absorptiometry and single-photon absorptiometry at the spine (anteroposterior, lateral), proximal femur, radius shaft, distal forearm, and the whole body. Bone mass parameters were analyzed using a quadratic regression model and segmented regression models with quadratic-quadratic or quadratic-linear form. The results show that most of the bone mass at multiple skeletal locations will be accumulated by late adolescence. This is particularly notable for bone mineral density of the proximal femur and the vertebral body. Bone mass of the other regions of interest is either no different in women between the age of 18 yr and the menopause or it is maximal in 50-yr-old women, indicating slow but permanent bone accumulation continuing at some sites up to the time of menopause. This gain in bone mass in premenopausal adult women is probably the result of continuous periosteal expansion with age. Since rapid skeletal mineral acquisition at all sites occurs relatively early in life, the exogenous factors which might optimize peak bone mass need to be more precisely identified and characterized.
Dual photon absorptiometry (DPA) of the lumbar spine (2nd, 3rd and 4th lumbar vertebrae) was carried out using a Norland 2600 bone densitometer on 194 Omani women (OW). The exclusion criteria were (1) any medical treatment known to affect calcium metabolism or bone mass, (2) osteomalacia or secondary osteoporosis, (3) the presence of osteophytes or compression fractures of the lumbar vertebrae and (4) the presence of aortic calcifications. The bone mineral density (BMD) results showed a peak value occurring in the 30-35 year old age range (mean 1.1 g cm-2, standard deviation 0.1). The data were compared with a group of 165 normal British women (BW) with a similar age distribution whose peak BMD (obtained with dual X-ray absorptiometry) occurred in the 40-45 year old age range. The two groups were compared in each 10 year age range and the BMD of the OW group was found to be significantly lower in the 40-49 year old age range (P < 0.01) as well as the 50-59 and 60-69 year old age ranges (P < 0.001).
The incidence of osteoporotic fractures increases with advancing age. Despite advances in therapy, reversal of bone loss in established osteoporosis remains problematic and deformities and disability due to fractures often persist. Therefore the logical approach to osteoporosis treatment is preventive. Risk of fracture is determined largely by bone density, which is the end result of peak value achieved at skeletal maturity and subsequent age- and menopause-related bone loss. Thus the determinants of peak bone density and bone loss require full characterization. Environmental and lifestyle factors are important determinants of bone density, particularly physical activity and diet. For example, muscle strength and physical fitness predict bone density, so that regular moderate exercise may help maintain bone mass but probably does not reverse loss. Long-term calcium intake appears to be important for achievement and maintenance of peak bone density, especially in males. Smoking and excessive alcohol intake are deleterious to bone mass. Cultural norms in diet, lifestyle and physical activity obviously have an impact on bone density. Genetic factors have a strong role in determining the wide range in 'normal' peak bone mass. Moreover we have found strong genetic determinants of rates of change of bone mass in the lumbar spine and similar trends for sites in the femoral neck. We have shown previously that genetic factors influence bone turnover indices, particularly osteocalcin. Investigating these relationships with restriction fragment length polymorphisms, we have identified variants of the vitamin D receptor gene which predict osteocalcin levels and presumably bone turnover.(ABSTRACT TRUNCATED AT 250 WORDS)
Low bone mass is known to be associated with an increased risk of fractures. Osteoporosis prevention by maximizing bone mass will be crucial and requires a better knowledge of bone mass acquisition during adolescence. Bone mass was assessed in 574 healthy volunteer females aged 10-24 years. Spine bone mineral density (BMD) in anteroposterior (AP L2-4) and lateral (LAT L3) views was measured using dual-energy X-ray absorptiometry (DXA) and AP bone mineral content (BMC) was calculated. At the same time, spine AP-BMD (L2-4) was evaluated in 333 normal menstruating women, aged 27-47 years. Bone values, osteocalcin and IGF-1 serum concentrations were correlated with chronological age, skeletal age, pubertal stages and time after menarche. In this cross-sectional study, AP- and LAT-BMD and BMC increased dramatically between skeletal ages 10 and 14 or until the first year after menarche. Between 14 and 17 skeletal years of age, AP-BMD and BMC increased moderately, whereas LAT-BMD remained unchanged. After skeletal age 17, or the fourth year after menarche, there was no significant increase in BMD or BMC, and their values did not differ from those of menstruating women. A serum osteocalcin peak was observed at skeletal ages 11-12 or at stage P3, whereas IGF-1 peaked at 13-14 skeletal years of age or at P4 and the first year after menarche. Eighty-six per cent of the adult bone mass of the spine is acquired before skeletal age 14 or the second year after menarche; therefore osteoporosis prevention programs will be particularly effective before that age.
The study of ethnic differences in bone mineral density (BMD) is helpful in understanding differences in osteoporosis and differences in fracture status. In this study, the trabecular BMD in Japanese women with and without spinal fracture was compared to that in American women with and without fracture. In the cross-calibration study, the quantitative computed tomography (QCT) systems used at the University of California San Francisco (UCSF) and at Nagasaki University showed excellent correlation. Normative BMD was assessed with the K2 HPO4 liquid phantom in 538 American aged 20-85 years, and with the B-MAS 200 phantom of Nagasaki in 577 Japanese aged 20-83 years. These BMD were adjusted for use with the Image Analysis solid phantom of UCSF using the result of cross-calibration. For investigation of the difference in BMD values relative to fracture status, trabecular BMD in 223 postmenopausal American women (55 with fracture), and in 225 postmenopausal Japanese women (67 with fracture) were compared. The absolute BMD values in Japanese were lower than those in American, and the differences were greater with advancing age. In premenopausal women, BMD began to decrease at age of 20 in Japanese, while the peak bone mass was maintained until age of 35 in American. In immediate postmenopausal women, BMD significantly decreased in both populations. In later postmenopausal women, BMD significantly decreased with age in Japanese, while BMD decreased less rapidly in American. The fracture threshold is considered lower in Japanese women. However, the BMD difference between American and Japanese women with fracture was similar to that without fracture. In conclusion, Japanese women are found to have a lower BMD and lower fracture threshold than American women. The significant decrease of spinal trabecular BMD in late postmenopause is potentially responsible for the higher prevalence of spinal fracture in Japanese women.
In order to analyze the role of the estrogen receptor (ER) gene allelic polymorphisms on bone mineral density (BMD), 173 pre- and postmenopausal women were divided into four groups according to their menstrual status (group A: premenopausal women; group B: late premenopausal women; group C: postmenopausal women who had menopause for 5 years or less; and group D: postmenopausal women who had menopause for more than 5 years), and the relationship between ER gene polymorphism and lumbar spine BMD, the percent annual change in BMD and biochemical markers were studied. The restriction fragment length polymorphism (RFLPs) were represented as Xx (XbaI) and Pp (PvuII), with upper case and lower case letters signifying the absence or presence of restriction sites, respectively. In group A, the Xx genotype had significantly higher BMD (p < 0.01) than the xx genotype, but the difference was lost in groups B, C, and D. Because the percent annual change in BMD of group A was 0.052% and was not statistically different among genotypes, it is suggested that RFLP by Xba I is closely linked with peak bone mass that was attained during the subject's late thirties. In group B, serum N-region osteocalcin (N-OC) levels and the percent annual change in BMD showed a significantly larger increase than that of group A, indicating postmenopausal bone loss had commenced. Because the N-OC level of the Xx genotype was significantly higher than that of the xx genotype (p < 0.05), and the percent annual change in BMD of the Xx genotype showed a tendency to increase (p = 0.072), it is suggested that the high BMD of the Xx genotype is rapidly lost during menopausal transition. There were no significant relationships between RFLP and BMD in groups C and D, and between RFLP and BMD in groups C and D, and between RFLP by PvuII and BMD. The present study suggests that the Xx genotype is involved in accretion of BMD during young adulthood, but the effect was lost during menstrual transition.
The recent development of methods for measuring bone mineral content in children has markedly improved our ability to determine changes in bone mass during growth. Currently, the three most generally accepted techniques for measuring the bones of children are dual-energy X-ray absorbtiometry (DXA), quantitative computed tomography (QCT) and quantitative ultrasound (QUS). These techniques vary considerably in their acquisition of data and comparisons between them are difficult and, more often than not, judgment regarding their value has been, at least partially, subjective. DXA is, by far, the most widely used technique for bone measurements. It is low in cost, accessible, easy to use, and provides an accurate and precise quantitation of bone mass in adults. Unfortunately, DXA is unable to account for the large changes in body and skeletal size that occur during growth, limiting its use in longitudinal studies in children. QCT can asses both the volume and the density of bone in the axial and appendicular skeletons, without influence from body or skeletal size, giving it a major advantage over other modalities for bone measurements in children. The cost and inaccessibility of CT scanners, however, has significantly limited its use for bone measurements. Measuring the bones of children by QUS is appealing because ultrasound is low in cost, portable, easy to use and does not emit radiation. In adults, this technique is able to predict fracture risk independent of bone mass determinations in patients with osteoporosis and, therefore, its measurements must be related to certain aspects of bone strength. However, ultrasound values are dependent on so many structural properties not yet fully understood, that it is difficult to use the information meaningfully in children.
To examine the effect of age on mineral metabolism and bone mineral density (BMD) of the hip and spine in Native American women.
A cross-sectional study.
The Sac and Fox Nation in rural Oklahoma
Serum measurements were made of 25 hydroxyvitamin D (25OHD), osteocalcin, and immunoreactive parathyroid hormone. Bone mineral density of the hip and spine was assessed by dual energy X-ray absorptiometry.
A total of 77 Native American women aged 19 to 85 years.
Serum 25 hydroxyvitamin D was related inversely to age (r = -0.32; P < .05) and was less than 15 ng/mL in 7% of the subjects. Serum osteocalcin was higher (P < .001) in postmenopausal than in premenopausal subjects. In postmenopausal subjects, serum osteocalcin was related to age (r = .59, P < .001). BMD was lower (P < .001) in postmenopausal than in premenopausal subjects. There was no evidence of bone loss before age 50 in either the femur or the spine. Age (r > or = -0.48, P < .001) and body mass index (BMI) (r > or = 0.41, P < .005) were independent determinants of both femoral and lumbar BMD. Serum 25OHD was a significant independent determinant of both lumbar (r = .26, P < .05) and femoral (r = .41, P < .01) BMD. Age, BMI, and serum 25OHD together accounted for 70% of the variance in BMD at these sites. The use of t scores indicated femoral bone density was higher (P < .05) in premenopausal Native American women, and lower (P < 0.05) in postmenopausal subjects, compared with white women.
In Native American women, there is a reduction in bone density and a sustained increase in bone turnover postmenopausally. BMI and serum 25OHD are significant determinants of BMD. Peak BMD may be higher, and the postmenopausal rate of bone loss greater, than that in white women.
A population-based study was performed in order to compare different definitions of peak bone mass, and to apply the corresponding T-scores for different skeletal sites to a cohort of 70-yr-old women for studying the prevalence of osteoporosis. Bone mineral density (BMD) of the hip, lumbar spine, and forearm was measured by dual X-ray absorptiometry (Hologic 4500) in 296 women ages 16-31 yr and 210 women age 70 yr. Peak bone mass occurred in women in their early 20s at the proximal femur and at 28 and 31 yr at the spine and forearm, respectively. BMD cutoff levels were compared to machine-specific cutoff values for the different sites. When applied to our cohort of 70-yr-old women, the prevalence of osteoporosis at the total hip was 9-25%, depending on which peak bone mass the T-score of -2.5 was based. The prevalence in the spine was 28-33% and in the forearm 45-67%. Osteoporosis in at least one of the three measured sites was documented in 49-72% of the population sample. Our results show that the use of T-score to define osteoporosis results in a highly different prevalence rate in a given population depending on the reference population and the skeletal sites chosen for measurement.
Risk of osteoporosis in later life may be determined during adolescence and young adulthood. The present study used longitudinal data to examine the accumulation of bone mineral content (BMC) and bone mineral density (BMD) in Caucasian subjects ages 6-36 yr. Growth in BMC and BMD (measured by dual X-ray absorptiometry; Lunar, Madison, WI) of 94 males and 92 females was monitored for a mean period of 4.29 yr. The main findings were that there were no sex differences in BMC or BMD during the prepubertal stage; however, females had significantly higher BMD of the pelvis and BMC and BMD of the spine during puberty, and postpubertal males generally had significantly higher BMC and BMD than their female counterparts. In addition, the longitudinal rate of bone accumulation in both sexes increased rapidly during childhood and adolescence and was nearly complete at the end of puberty. Finally, peak BMC and BMD was achieved between the ages of 20 and 25 and occurred earlier in females than in males. The rates of growth and timing of peak bone mass as reported here define the crucial period during which intervention protocols should be developed for maximizing skeletal mass to prevent the development of osteoporosis.
Achievement of higher peak bone mass early in life may play a critical role against postmenopausal bone loss. Bone mineral density (BMD) of the spine, femoral neck, greater trochanter, Ward's triangle, and spine bone mineral content (BMC) and bone surface area (BSA) were assessed by dual energy x-ray absorptiometry in 300 healthy females (age 6-32 years). Bone measurements were described by using nonlinear models with age, weight, height, or dietary calcium intake as the explanatory variables. At the spine, femoral neck, greater trochanter, and Ward's triangle, the highest BMD level was observed at 23.0 +/- 1.4, 18.5 +/- 1.6, 14.2 +/- 2.0, and 15.8 +/- 2.1 years, respectively. The age of attaining peak spine BMC and BSA cannot be estimated, as significant increases in these two measures were observed through this age group. Age, weight, and height were all significant predictors of all these bone measurements. Weight was a stronger predictor than age for all sites. Dietary calcium intake was not a significant predictor for any of these bone measurements. We conclude that age of attaining peak bone mass at the hip is younger than at the spine, and BMC and BSA at the spine continue to increase through the early thirties in females.
The effect that growth has on dual-energy x-ray absorptiometry (DXA) bone measurements is yet to be fully defined. The purpose of this study was to determine the best method for optimizing pediatric bone measurements using DXA. Height, weight, body mass index, skeletal age, and Tanner stage of sexual development were determined for 64 healthy boys and 60 healthy girls ages 6-17 yr. DXA of the lumbar vertebrae was performed to measure bone mineral content (BMC, grams) and areal bone mineral density (aBMD, grams per square centimeter), and geometric corrections were used to calculate volumetric bone mineral densities (vBMD): vBMD1 = aBMD/ radical(DXA-area) and vBMD2 = aBMD/bone height. Computed tomography (CT) imaging was performed to measure volumetric bone density (vBD) and vertebral volume (Vol) and to calculate CT-BMC = vBD * Vol. Linear regression was used to compare DXA-BMC vs. CT-BMC and CT vBD vs. DXA aBMD, vBMD1, and vBMD2. Multiple regression including the anthropometric and developmental parameters was also performed. DXA and CT BMC were highly correlated (r2= 0.94). However, DXA aBMD correlated more strongly with CT Vol (r2= 0.68) than with CT density (r2= 0.39), and calculation of DXA volumetric densities only slightly improved the density correlations (r2= 0.49 for vBMD1; r2= 0.55 for BMD2). The correlations for density were particularly poor for subjects in Tanner stages 1-3 (r2= 0.02 for aBMD; r2= 0.13 for vBMD1; r2= 0.27 for vBMD2). In contrast, multiple regression accounting for the anthropometric and developmental parameters greatly improved the agreement between the DXA and CT densities (r2= 0.91). These results suggest that DXA BMC is a more accurate and reliable measure than DXA BMD for assessing bone acquisition, particularly for prepubertal children and those in the early stages of sexual development. Use of DXA BMD would be reasonable if adjustments for body size, pubertal status, and skeletal maturity are made, but these additional assessments add significant complexity to the studies.
The age at which peak bone mineral content (peak BMC) is reached remains controversial and the mechanism underlying bone mass "consolidation" is still undefined. The aims of this study were to investigate; (1) the timing of peak BMC by studying bone size and volumetric BMD (vBMD) as separate entities and (2) to determine the relative contributions of bone size and vBMD to bone mass "consolidation". A total of 132 healthy Caucasian children (63 boys and 69 girls, ages 11-19 years) and 134 healthy Caucasian adults (66 men and 68 women, ages 20-50 years) were studied. BMC was measured by DXA at the AP and lateral lumbar spine (LS) femoral neck (FN) and ultradistal radius (UDR). vBMD and bone volume (size) were estimated. Bone mass "consolidation" was examined between age 16 years to the age peak bone values were attained. During growth, BMC and bone size increased steeply with age and approximately 80-90% of peak values were achieved by late adolescence. vBMD at the spine and UDR (in women) increased gradually, but vBMD at the FN and UDR in men remained almost constant. During "consolidation", bone size continued to increase with little change in vBMD. Peak vBMD at the lumbar spine was reached at 22 and 29 years in men and women, respectively, but earlier at the FN at 12 years. At the UDR peak vBMD was achieved at age 19 years in women, with little change in men. In conclusion, peak vBMD and bone size are almost fully attained during late adolescence. Although speculative, the lack of change in vBMD during consolidation implies that the continued increase in bone mass may primarily be due to increases in bone size rather than increases in either trabecular volume, cortical thickness or the degree of mineralisation of existing bone matrix (vBMD). Skeletal growth and maturation is heterogeneous, but crucial in understanding how the origins of osteoporosis may begin during childhood and young adulthood.
- Rr Recker
- Km Davies
- Sm Hinders
- Rp Heaney
- Mr Stegman
- Db Kimmel
Recker RR, Davies KM, Hinders SM, Heaney RP, Stegman MR, Kimmel DB
1992 Bone gain in young adult women. JAMA 268:2403–2408
Spinal trabecular bone loss and fracture in American and Japanese women.
- Ito
Bone acquisition in healthy children and adolescents: comparisons of DXA and CT measures.
- Wren
Bone mineral measurement with special reference to precision, accuracy, normal values, and clinical relevance
- Christiansen
Variations in osteoblastic activity with age
- Villaneuva