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Osteoporosis, a unitary hypothesis of collagen loss in skin and bone
Abstract
Progress in osteoporosis has been stultified by repetitive, statistic-driven studies and catechistic reviews; in the absence of concept and hypothesis research is aimless, and the trivial associations it continually reveals, has led to the cul-de-sac of multifactorialism. A return to hypothesis-led research which seeks major causal defects and the conclusive therapies that arise from them is essential. The hypothesis proposed evolved from research into the mechanism of senile purpura. This predicted a causal loss of skin collagen that was contrary to contemporary opinion, but was confirmed when collagen was expressed absolutely, instead as a percentage or ratio: women have less collagen than men and it decreases by 1% a year in exposed and unexposed skin. Corticosteroids (which also produce shear purpura) reduce skin collagen and androgen and virilism increase it; growth hormone produces the greatest increase, and there is a decrease in hypopituitarism. All these changes in skin collagen correspond to changes in bone density, and the circumstances are too various for coincidence. This led to the hypothesis that the changes found in skin collagen also occur in bone collagen, leading to the associated changes in bone density; thus a loss of collagen in skin and bones with aging is the causal counterpart to loss of bone density in senile osteoporosis. If this is correct then, as with aging, androgen and virilisation, corticosteroids, growth hormone and hypopituitarism, changes in bone density should correspond to systemic changes in skin collagen. This correspondence is found to occur in osteogenesis imperfecta and Ehlers-Danlos syndrome, two genetically discrete families of disordered collagen production, and other situations, e.g., scurvy and homocystinuria. A primary loss of collagen in osteoporotic bones is an essential prediction of the hypothesis; in fact this loss is well established but, inexplicably, it has been assumed to be secondary to the bone loss. Because of the comparable changes in skin and bones, the hypothesis implies that skin collagen could be used to predict the state of the bones and their response to treatment. It also implies androgen should be an effective treatment of osteoporosis, and growth hormone even more effective (likewise, of course, skin aging). More importantly, skin collagen and the production of collagen by skin fibroblasts could be used for the assay and industrial development of more potent, if not less toxic treatments and prevention of loss of bone (and skin) substance.
... In fact, collagen in the skin and bone decreases with aging, corticosteroid treatment (22), the decline of estrogen (6)(7)(8)11) and growth hormones (12,13), and advanced glycation end-product deposition, causing degradation of collagen cross-linking structures (23-26). Aging-induced collagen loss causes yellowing, browning, poor elasticity, deeper wrinkles, wrinkling, and thinning, reflecting the atrophy of the collagenous dermis in the skin and osteoporosis in the bones (23, 24,27). Age-related alterations in the dermis demonstrate disruptions in the elastic fiber network and a reduction in the number of collagen fiber bundles (28). ...
... In addition, acromegaly (35) and pachydermoperiostosis (36)(37)(38)(39), which produce skin thickening (increase in skin collagen), bone hypertrophy (increase in bone density), hypopituitarism, Cushing's syndrome, anorexia nervosa (40), and osteogenesis imperfecta, result in skin thinning and bone atrophy (35,41,42). Skin collagen increase/decrease correlates with BMD (27). ...
The phrase “skin as a mirror of internal medicine,” which means that the skin reflects many of the diseases of the internal organs, is a well-known notion. Despite the phenotypic differences between the soft skin and hard bone, the skin and bone are highly associated. Skin and bone consist of fibroblasts and osteoblasts, respectively, which secrete collagen and are involved in synthesis, while Langerhans cells and osteoclasts control turnover. Moreover, the quality and quantity of collagen in the skin and bone may be modified by aging, inflammation, estrogen, diabetes, and glucocorticoids. Skin and bone collagen are pathologically modified by aging, drugs, and metabolic diseases, such as diabetes. The structural similarities between the skin and bone and the crosstalk controlling their mutual pathological effects have led to the advocacy of the skin–bone axis. Thus, the skin may mirror the health of the bones and conversely, the condition of the skin may be reflected in the bones. From the perspective of the skin–bone axis, the similarities between skin and bone anatomy, function, and pathology, as well as the crosstalk between the two, are discussed in this review. A thorough elucidation of the pathways governing the skin–bone axis crosstalk would enhance our understanding of disease pathophysiology, facilitating the development of new diagnostics and therapies for skin collagen-induced bone disease and of new osteoporosis diagnostics and therapies that enhance skin collagen to increase bone quality and density.
... If collagen (organic matter) is a key factor in skeletal ductility and toughness, then reliable biomarkers that can be easily used in clinical practice are required. In this context, Shuster [34,35] proposed a theory of cross-aging between bone and skin by assuming that the collagen in these two connective tissues ages at the same rate. In fact, the degradation of structural [36,37], mechanical [38], textural [39], functional, and physiological [40] aspects of the skin are now well documented between young and elderly populations, and some of the manifestations reported are similar to those of bone aging. ...
... Assuming that body collagen ages equally, the skin dermis and bone collagen should demonstrate the same kinetics [34,35]. As early as 60 years ago, McConkey et al. reported that the atrophy of the dorsal skin of the hands was qualitatively correlated with osteoporosis [52]. ...
The mechanical properties of bone tissue are the result of a complex process involving collagen–crystal interactions. The mineral density of the bone tissue is correlated with bone strength, whereas the characteristics of collagen are often associated with the ductility and toughness of the bone. From a clinical perspective, bone mineral density alone does not satisfactorily explain skeletal fragility. However, reliable in vivo markers of collagen quality that can be easily used in clinical practice are not available. Hence, the objective of the present study is to examine the relationship between skin surface morphology and changes in the mechanical properties of the bone. An experimental study was conducted on healthy children (n = 11), children with osteogenesis imperfecta (n = 13), and women over 60 years of age (n = 22). For each patient, the skin characteristic length (SCL) of the forearm skin surface was measured. The SCL quantifies the geometric patterns formed by wrinkles on the skin’s surface, both in terms of size and elongation. The greater the SCL, the more deficient was the organic collagen matrix. In addition, the bone volume fraction and mechanical properties of the explanted femoral head were determined for the elderly female group. The mean SCL values of the healthy children group were significantly lower than those of the elderly women and osteogenesis imperfecta groups. For the aged women group, no significant differences were indicated in the elastic mechanical parameters, whereas bone toughness and ductility decreased significantly as the SCL increased. In conclusion, in bone collagen pathology or bone aging, the SCL is significantly impaired. This in vivo skin surface parameter can be a non-invasive tool to improve the estimation of bone matrix quality and to identify subjects at high risk of bone fracture.
... Of note, type V collagen, which is found in skin, cornea, and bone, has a fundamental role in type I collagen fibrillogenesis, forming a core inside major collagen fibrils. Its deficiency in cEDS should result in the misalignment of the collagen molecules and fibers, which are required for adequate bone mineralization [28]. Therefore, type V collagen alterations may also be hypothesized to result in a reduction of bone resistance and osteoporosis [28]. ...
... Its deficiency in cEDS should result in the misalignment of the collagen molecules and fibers, which are required for adequate bone mineralization [28]. Therefore, type V collagen alterations may also be hypothesized to result in a reduction of bone resistance and osteoporosis [28]. So far, however, a precise genotype/bone phenotype correlation in EDS patients was not reported. ...
Ehlers–Danlos syndrome (EDS) is an emerging cause of skeletal fragility. Mechanism of bone damage are probably multifactorial in line with the different skeletal phenotypes that can be found in clinical practice. A structured approach to clinical management of bone metabolic complication in EDS is proposed.
... 9 These observations led to a hypothesis that skin thinning and bone loss could be correlated. 10 Recent investigations suggest that the processes involved in chronological atrophy of both tissues may overlap, thereby providing a foundation for further investigations. 11 Correlation between skin and bone parameters in women with postmenopausal osteoporosis: a systematic review Given the importance of an early diagnosis of osteoporosis, the development of a probabilistic model to identify the persons at most risk in a certain population would have a great interest. ...
... Hence, assuming that all the collagen of the body will age equally, it is possible that skin and bone will age in the same manner, especially in postmenopausal osteoporosis. 10 Bone mass and skin collagen content share comparable regressive changes during ageing. Some authors have pointed out that skin collagen is influenced by the loss of oestrogen production by the ovaries and that skin collagen content decreases in the postmenopausal years. ...
Skin and bone share similarities in terms of biochemical composition.
Some authors have hypothesized that their properties could evolve concomitantly with age, allowing the estimation of the parameters of one from those of the other.
We performed a systematic review of studies reporting the correlation between skin and bone parameters in women with postmenopausal osteoporosis.
Fourteen studies – including 1974 patients – were included in the review.
Three of these studies included two groups of participants – osteoporotic and non-osteoporotic – in order to compare skin parameters between them: two studies found a significant difference between the two groups and one did not.
Eleven of these studies included one population of interest and compared its skin and bone parameters in a continuous manner: eight studies compared dermal thickness to bone mineral density (seven found a significant correlation [R = 0.19–0.486] and one did not); two studies compared skin elasticity to bone mineral density (both found a significant correlation [R = 0.44–0.57); and one study compared skin collagen to bone mineral density and found a significant correlation (R = 0.587).
It can be assumed that the estimation of skin alterations from ageing could help in estimating concomitant bone alterations.
Cite this article: EFORT Open Rev 2018;3:449-460. DOI: 10.1302/2058-5241.3.160088
... DS contains rich collagen with a content of 82.12% [16]. Collagen constitutes a family of proteins presenting in the extracellular matrices, taking up about 25% to 35% of the whole-body 2 Evidence-Based Complementary and Alternative Medicine protein content; unfortunately, our body loses collagen at a rate of 1% per year, starting at the age of 25 [17]. It is ubiquitous that collagen is responsible for maintaining the structural integrity of vertebrates and many other multicellular organisms [18], such as skin, tendons, ligaments, and cartilage. ...
... Postmenopausal bone loss is characterized by a decrease in BMD and a microarchitecture deterioration of trabecular bone, with a particular diminution in the total number of trabecular and an increase in the number of their perforations [25]. Shuster [17] reported that a loss of collagen in skin and bones with aging was the causal counterpart to loss of bone density in senile osteoporosis. According to results of experiment, the collagen peptide supplement significantly increased the BMD of the femur in ovariectomized rats ( Figure 2). ...
Deer sinew (DS) has been used traditionally for various illnesses, and the major active constituent is collagen. In this study, we assessed the effects of collagen peptide from DS on bone loss in the ovariectomized rats. Wister female rats were randomly divided into six groups as follows: sham-operated (SHAM), ovariectomized control (OVX), OVX given 1.0 mg/kg/week nylestriol (OVX + N), OVX given 0.4 g/kg/day collagen peptide (OVX + H), OVX given 0.2 g/kg/day collagen peptide (OXV + M), and OVX given 0.1 g/kg/day collagen peptide (OXV + L), respectively. After 13 weeks of treatment, the rats were euthanized, and the effects of collagen peptide on body weight, uterine weight, bone mineral density (BMD), serum biochemical indicators, bone histomorphometry, and bone mechanics were observed. The data showed that BMD and concentration of serum hydroxyproline were significantly increased and the levels of serum calcium, phosphorus, and alkaline phosphatase were decreased. Besides, histomorphometric parameters and mechanical indicators were improved. However, collagen peptide of DS has no effect on estradiol level, body weight, and uterine weight. Therefore, these results suggest that the collagen peptide supplementation may also prevent and treat bone loss.
... Diversos estudos constataram essa tendência, entretanto, as medidas cutâneas sozinhas não se mostraram suficientes para a precisa estimativa da densidade mineral. [7][8][9][10][11][12] Os autores objetivam avaliar a correlação entre a espessura da pele do dorso das mãos e a densidade óssea de mulheres adultas, assim como sua relação com os principais fatores de risco para osteoporose. ...
... A variação da espessura da pele do dorso das mãos entre mulheres adultas correlacionou-se de forma significativa com a variação da DMO lombar e do fêmur, independentemente dos demais fatores de risco, corroborando achados de estudos similares, e sugerindo que as alterações ósseas ocorram paralelamente ao envelhecimento cutâneo, provavelmente, pela atividade das colagenases desses órgãos (Quadro 1). 7,15 A pequena magnitude da correlação entre espessura da pele e os dados da DMO evidencia o caráter multifatorial da osteoporose, incluindo o componente genético e forte influência de elementos externos no desenvolvimento da doença. Os demais fatores de risco identificados nesse estudo são consoantes aos encontrados em pesquisas epidemiológicas para essa faixa etária, não existindo um modelo de risco ideal para sua estimativa na população. ...
Osteoporosis mainly affects menopausal women and the elderly, predisposing these individuals to fractures that result in morbidity, mortality and costs to the healthcare system. Since dermal collagen reduces in parallel with a decrease in bone mass with aging, skin thickness may be indicative of a risk of osteoporosis.
To evaluate the correlation between bone density and skin thickness on the backs of the hands of adult women.
A cross sectional study involving adult women attending a university hospital outpatient clinic who were interviewed individually and submitted to bone densitometry and measurement of skin thickness on the backs of their hands using skinfold calipers. Other risk factors for osteoporosis were also investigated.
A total of 140 patients were evaluated. Mean age (± standard deviation) was 57 ± 11 years. Mean skin thickness on the backs of the hands was 1.4 ± 0.4 mm. There was a correlation between the right and left hands (R = 0.9; p<0.01). A direct correlation was found between skin thickness on the backs of the hands and bone density at the lumbar spine and femur (p<0.01). These results remained consistent even following adjustment for the covariables of age, skin phototype, body mass index, smoking, use of oral corticoids, anti-inflammatory use and time since menopause. Osteoporosis was inversely associated with the thickness of the skin on the back of the hands (odds ratio = 0.10; p<0.03)
An independent correlation was found between skin thickness and bone density, suggesting that these events occur simultaneously. Skin signs may represent a non-invasive method of stratifying risk in these patients, helping identify cases requiring early treatment.
... 9 Hence, it is hypothesized that with the assumption that all collagen of the body would alter equally, the skin and bone are expected to act in the same manner, particularly in postmenopausal osteoporosis. 11,18,19 A decline in collagen and disorganization of the elastic fibers is observed through skin aging, resulting in skin thinning and wrinkling. 20 Furthermore, bone mass regresses through aging, accelerating in the postmenopausal era. ...
Introduction: Osteoporosis is a systemic disease that leads to mechanical fractures by decreasing bone density. Postmenopausal women with fractures following osteoporosis reportedly have thinner skin. This study evaluated the relationship between bone density and facial wrinkles. Methods: We conducted an analytical-cross-sectional study featuring 427 patients aged 40–80 referred to a bone density measurement center in Yazd in 2021. Demographic and clinical data were collected using a questionnaire. A dermatologist assessed wrinkles in 11 zones of the face as per the Lemperle scale. Results: The mean age of the participants was 69.63 years, with a slight female predominance noted (57%). The mean lumbar T-score was -2.69 ± 0.71, and the mean femoral T-score was -2.69 ± 0.72. Facial wrinkles increased with age and negatively correlated with lumbar and femoral T-scores. The findings were replicated after adjusting for other effective risk factors such as connective tissue/bone disorders, diabetes, corticosteroid use, and smoking. Conclusion: The increase in facial wrinkles with aging was associated with a decline in bone density in those at risk of osteoporosis. This observation could assist in accounting for facial wrinkles as a risk factor for osteoporosis, so that earlier diagnosis and intervention could be initiated. Longitudinal studies should further investigate this association
... Moreover, collagen is the most abundant protein in the human body and type I collagen accounts for 90% of the matrix of bone tissue, 85% of the matrix of dentin, 90% of the dermis, and a large part of the abdominal wall and tendons. Based on the hypothesis posed as early as 2005 by Shuster et al. regarding the theory of cross-ageing between all living tissues, according to which quantitative and qualitative alterations of collagen related to intrinsic ageing would occur at the same rate in internal and cutaneous tissues [39,40], characteristic length could be a marker of ageing that completes the markers of quality of other internal dense connective tissues. In conclusion, this study proposed an original diagnostic tool based on morphometric indices of the skin surface to have insights into collagen and elastin content in the dermis. ...
Objective: The main objective of this study was the development of a non-invasive mathematical marker of the skin surface, the characteristic length, to predict the microstructure of the dermis. This marker, at the individual level, is intended to provide the biological age of the patient in the context of personalised medicine for the elderly. Study design: To validate this hypothesis, a clinical study was conducted on 22 women over 60 years old from a population of osteoporotic subjects who sustained a femoral neck fracture: a morphological analysis of the skin surface was performed on the patient’s forearm and quantitatively compared with microarchitectural parameters of the dermis. Major results: The Elastin-to-Collagen ratio measured on dermis samples ranged between 0.007 and 0.084, with a mean of 0.035 ± 0.02. The surface characteristic length ranged between 0.90 and 2.621, with a mean of 0.64 ± 0.51. A very strong correlation was found between this characteristic length and the Elastin-to-Collagen ratio (r = 0.92). Conclusions: This study proposes an original diagnostic tool based on morphometric indices of the skin surface and shows a direct quantitative relationship with the dermis microarchitecture and its collagen and elastin content. The proposed method allows reliable and easy access to the intrinsic ageing of the dermis, which would be a strong biomarker in a personalised collagen treatment approach.
... These impact on the biophysical properties and regenerative capacity of the tissue and predispose to disease (Kim et al., 2015). In bone, the accumulation of AGEs, combined with collagen loss and cellular senescence, are regarded as critical drivers of osteoporosis (Sanguineti et al., 2014;Shuster, 2005). Loss of type II collagen turnover in mature cartilage is thought to predispose to poor regenerative capacity and OA. ...
Collagen-rich tissues have poor reparative capacity that predisposes to common age-related disorders such as osteoporosis and osteoarthritis. We used in vivo pulsed SILAC labelling to quantify new protein incorporation into cartilage, bone, and skin of mice across the healthy life course. We report dynamic turnover of the matrisome, the proteins of the extracellular matrix, in bone and cartilage during skeletal maturation, which was markedly reduced after skeletal maturity. Comparing young adult with older adult mice, new protein incorporation was reduced in all tissues. STRING clustering revealed changes in epigenetic modulators across all tissues, a decline in chondroprotective growth factors such as FGF2 and TGFβ in cartilage, and clusters indicating mitochondrial dysregulation and reduced collagen synthesis in bone. Several pathways were implicated in age-related disease. Fewer changes were observed for skin. This methodology provides dynamic protein data at a tissue level, uncovering age-related molecular changes that may predispose to disease.
... The long half-life of type II collagen within cartilage is thought to account for the observed limited repair capacity of the tissue (7). In bone, the accumulation of AGEs, combined with collagen loss and cellular senescence, are regarded as critical drivers of osteoporosis (8,9). Collagens also play an essential role in wound healing; their deposition and quality define wound closure and resulting tensile strength of the scar. ...
Collagen-rich tissues have poor reparative capacity that is further impaired with age, predisposing to common age-related disorders such as osteoporosis and osteoarthritis. We used in vivo pulsed SILAC labelling to quantify new protein incorporation into cartilage, bone, skin and plasma of mice across the life course. We report highly dynamic matrisome turnover in bone and cartilage during skeletal maturation, which was markedly reduced after skeletal maturity. Comparing young adult with older adult mice, new protein incorporation was reduced in all tissues. STRING clustering revealed epigenetic modulation across all tissues, a decline in chondroprotective growth factors such as FGF2 and TGFb in cartilage, and clusters indicating mitochondrial dysregulation and reduced collagen synthesis in bone. Several of these pathways have been associated with age-related disease. Fewer changes were observed for skin and plasma. This methodology provides dynamic protein data at a tissue level, uncovering age-related molecular changes that may predispose to disease.
... Adequate silicon concentration is required for the activation of prolyl hydroxylase that catalyzes the proline residues of collagen chains which is a critical step in collagen type-I synthesis and its secretion into the extracellular space. [3,14] Prolyl hydroxylase enzyme gets activated by silicon in osteoblast cytoplasmic granular endoplasmic reticulum followed by bone formation and mineralization. [15] consequence of sIlIcon defIcIency on Bone health [fIguRe 1] [16,17] ...
... 4 Confirmation would require 'studies of the absolute collagen content of skin and bones', 4 but the simple first test was the predicted correlation between skin collagen and bone density. Total skin collagen content was measured in patients with various skin, endocrine and genetic conditions, [4][5][6][7][8][9][10][11][12][13] and they all confirmed the correlation, and with the causal strength of a dose-response relationship for age and oral corticosteroids. Patients with Cushing's syndrome had a greatly reduced skin collagen and bone density; 7 patients with acromegaly 11 had a massive increase in skin collagen (an effect missed when collagen was expressed as a percentage) and their bones were dense; in contrast, skin collagen content was reduced in patients with hypopituitarism 11 and their bones were thinned. ...
... Collagen is a protein that provides a framework for soft tissue which calcium adheres onto, creating a hardened framework [16]. Shuster reported that collagen loss in skin and bones with aging is the causal counterpart to bone density loss in senile osteoporosis [26]. In the present study, CH intake trended to increase the Hyp content in bone, with significant differences observed between the MCCH and M groups. ...
Osteoporosis is a common skeletal disorder in humans and gelatin hydrolysates from mammals have been reported to improve osteoporosis. In this study, 13-month-old mice were used to evaluate the effects of collagen hydrolysates (CHs) from silver carp skin on osteoporosis. No significant differences were observed in mice body weight, spleen or thymus indices after daily intake of antioxidant collagen hydrolysates (ACH; 200 mg/kg body weight (bw) (LACH), 400 mg/kg bw (MACH), 800 mg/kg bw (HACH)), collagenase hydrolyzed collagen hydrolysates (CCH) or proline (400 mg/kg body weight) for eight weeks, respectively. ACH tended to improve bone mineral density, increase bone hydroxyproline content, enhance alkaline phosphatase (ALP) level and reduce tartrate-resistant acid phosphatase 5b (TRAP-5b) activity in serum, with significant differences observed between the MACH and model groups (p < 0.05). ACH exerted a better effect on osteoporosis than CCH at the identical dose, whereas proline had no significant effect on repairing osteoporosis compared to the model group. Western blotting results demonstrated that CHs mainly increased bone remodeling by stimulating the transforming growth factor β1 (TGF-β1)/Smad signaling pathway and improving the interaction between collagen and α2β1 integrin. The results indicated that CHs from fish could be applied to alleviate osteoporosis or treat bone loss.
... Collagen, the source of fibers is the most abundant constituent of all the connective tissue. It contains approximately 20% to 40% of the total body proteins of extracellular matrix compartment [45]. Numerous scientific studies reported that osteoporosis has become a major health issue. ...
The aim of this study was to assess the effect of Consciousness Energy Healing-based vitamin D3 and DMEM medium on bone health parameters such as alkaline phosphatase (ALP), collagen, and bone mineralization in human bone osteosarcoma cells (MG-63). The test items (vitamin D3 and DMEM), were divided into two parts. One part of each sample was received the Biofield Energy Treatment by Elizabeth Patric and those samples were denoted as the Biofield Energy Treated (BT) samples, while the other parts of each sample were referred as the untreated test items (UT). The MTT cell viability assay revealed that the test samples were found as safe in the tested concentrations. The experimental results showed that the level of ALP was remarkably increased by 88.62% and 70.48% in the BT-DMEM + UT-Test item (UT-TI) and BT-DMEM + BT-TI groups, respectively at 10 µg/mL compared to the UT-DMEM + UT-TI group. Moreover, the collagen level was significantly increased by 252.59%, 50.55%, and 94.99% in the UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI groups, respectively at 10 µg/mL compared to the UT-DMEM + UT-TI group. Further, the collagen level was significantly increased by 120.90% and 72.66% in the UT-DMEM + BT-TI and BT-DMEM + UT-TI groups, respectively at 50 µg/mL, while 34.99% in the UT-DMEM + BT-TI at 100 µg/mL compared to the untreated group. Apart from this, the percent of bone mineralization was distinctly enhanced by 127.13%, 225.12%, and 106.28% in the UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI groups, respectively at 0.1 µg/mL compared to the untreated group. Moreover, the percentage of bone mineralization was significantly increased by 52.86%, 67.00%, and 23.62% in the UT-DMEM + BT-TI, BT-DMEM + UT-TI, and BT-DMEM + BT-TI groups, respectively at 1 µg/mL compared to the untreated group. Additionally, the percentage of bone mineralization was significantly increased by 46.57% and 51.36% in the UT-DMEM + BT-TI and BT-DMEM + UT-TI groups, respectively at 10 µg/mL compared to the untreated group. Altogether, the Biofield Energy Treated vitamin D3 was significantly improved the bone health parameters and it could be an alternative approach for nutraceutical supplement to combat vitamin D3 deficiency and able to fight against various bone-related disorders including rickets, low bone density, osteomalacia, bone and joint pain, bone fractures, osteoporosis, osteoma, osteogenesis imperfecta, Paget’s disease, deformed bones, chondrodystrophia fetalis, stress management and prevention, autoimmune and inflammatory diseases, and anti-aging by improving overall health.
... Type 1 collagen is the most abundant in all the connective tissue. Collagen is comprised of about 25% to 35% of the total body proteins, mainly distributed in the extracellular matrix compartment [42]. From literature, it is well established that collagen is responsible for maintaining the structural integrity of various organs such as skin, tendons, ligaments, cartilages etc. in the vertebrates and multicellular organisms [10]. ...
The study objective was to investigate the effect of Consciousness Energy Healing-based vitamin D3 and DMEM medium on bone health. The test items (vitamin D3 and DMEM), were divided into two parts. One part of each sample was received the Biofield Energy Treatment by Debra Jane Schnitzer and those samples were denoted as the Biofield Energy Treated (BT) samples, while the other parts of each sample were referred as the untreated test items (UT). Parameters such as ALP, collagen, and bone mineralization were performed to evaluate the bone strength in human bone osteosarcoma cells (MG-63). The test samples were found as safe in the tested concentrations by MTT cell viability assay. ALP was significantly increased by 27.75%, 28.21%, and 60% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 50 µg/mL compared to the UT-DMEM + UT-Test item group. Moreover, the ALP level was significantly raised by 11.17% and 74.57% in the UT-DMEM + BT-Test item and BT-DMEM + BT-Test item groups, respectively at 100 µg/mL compared to the UT-DMEM + UT-Test item group. Collagen was significantly increased by 54.53% and 115.01% in the UT-DMEM + BT-Test item and BT-DMEM + UT-Test item groups, respectively at 0.1 µg/mL compared to the untreated group. Further, the collagen level was significantly increased by 131.87% (at 1 µg/mL) and 179.77% (at 10 µg/mL) in the UT-DMEM + BT-Test item group compared to the untreated group. Apart from this, the percent of bone mineralization was distinctly increased by 75.94%, 125.79%, and 117.38% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 10 µg/mL compared to the untreated group. Additionally, the percentage of bone mineralization was significantly increased by 46.08%, 173.22%, and 171.17% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 50 µg/mL compared to the untreated group. Altogether, the Biofield Energy Treated vitamin D3 was significantly improved the bone health parameters and it could be an alternative approach for nutraceutical supplement to combat vitamin D3 deficiency and able to fight against various bone-related disorders including rickets, low bone density, osteomalacia, bone and joint pain, bone fractures, osteoporosis, osteoma, osteogenesis imperfecta, Paget’s disease, deformed bones, chondrodystrophia fetalis, stress management and prevention, autoimmune and inflammatory diseases, and anti-aging by improving overall health.
... Известна тесная зависимость между дефицитом эстрогенов и снижением содержания и нарушением структуры коллагена кожи [4][5][6][7]. В течение первых 15 лет постменопаузы происходит ежегодное снижение содержания коллагена в коже на 2,5%, этот процесс идет параллельно со снижением минеральной плотности костей [8]. У женщин с ранней менопаузой наблюдаются и дегенеративные изменения эластиновых волокон дермы [9]. ...
Results of studying of efficiency and safety of the combination of medicine Ci-Clim and cosmetic product Ci-Clim (JSC EVALAR, Russia), containing extract of cimicifuga racemosa, for the purpose of correction of structural and functional changes of skin of women in the perimenopausal, menopausal and postmenopausal period are presented. Materials and methods. Under supervision there were 15 women aged from 41 till 56 years, who had any signs of a climacteric syndrome. Research of the morphologic and functional skin characteristics (including measurement of thickness of derma and epidermis by means of ultrasound, the characteristic of structure, humidity, elasticity and visual appearance of skin), and also an assessment of quality of life by means of SF-36 questionnaire was conducted. Patients were treated with combination of medicine Ci-Clim 1 tablet 2 times per day during meal within 12 months, and cosmetic product Ci-Clim on the face (1 ml 2 times a day) daily within 12 months. Repeated visits were performed monthly, an assessment of the morphological and functional properties of the skin were done at 6 and 12 months.Results. Significant reduction of thickness of epidermis and increase in thickness of derma, and also increase of skin humidity and elasticity were noted at 6 and 12 months. Visual characteristics of skin improved. Quality of life of postmenopausal women improved as well as the skin characteristics. Conclusion. Application of the combination of medicine Ci-Clim and cosmetic product Ci-Clim, containing herbal extracts is highly effective, safe and well tolerated drug that allows to achieve effect in treatment of involutional changes of skin, improving an emotional state and quality of life of women.
... Type 1 collagen is the most abundant in all the connective tissue. Collagen is comprised of about 25% to 35% of the total body proteins, mainly distributed in the extracellular matrix compartment [42]. From literature, it is well established that collagen is responsible for maintaining the structural integrity of various organs such as skin, tendons, ligaments, cartilages etc. in the vertebrates and multicellular organisms [10]. ...
... Collagen comprises about 25% to 35% of the total body proteins content, mainly distributed in the extracellular matrix compartment. Naturally, after the age of 25 years body start to loses collagen at the rate of 1% per year [48]. It is well established that collagen is responsible for maintaining the structural integrity of various organs such as skin, tendons, ligaments, cartilages etc. in the vertebrates and multicellular organisms. ...
The objective of this study was to assess the potential of Biofield Energy Treated vitamin D3 and DMEM medium on bone health. The test items, were divided into two parts. One part of each sample received the Consciousness Energy Healing Treatment by Bonnie Patrice Hegarty-Diaz and those samples were labeled as the Biofield Energy Treated (BT) samples, while the other parts of each sample were denoted as the untreated test items (UT). Various parameters were performed to evaluate bone strength and integrity such as ALP, collagen, and bone mineralization in human bone osteosarcoma cells (MG-63). The test samples were found as safe in the tested concentrations by MTT assay. ALP was significantly increased by 50.77% and 50.27% in the BT-DMEM + UT-Test item and BT-DMEM + BT-Test item, respectively at 10 µg/mL compared to the UT-DMEM + UT-Test item group. Further, the ALP level was significantly elevated by 137.29% and 88.08% and 107.93% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 50 µg/mL compared to the UT-DMEM + UT-Test item group. Further, the collagen level was significantly increased by 66.15%, 88.18%, and 55.87% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item and BT-DMEM + BT-Test item, respectively at 0.1 µg/mL compared to the untreated group. Collagen was significantly increased by 39.44%, 39.44%, and 49.66% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 50 µg/mL compared to the untreated group. Additionally, the percent of bone mineralization was distinctly increased by 13.51% and 47.21% in the UT-DMEM + BT-Test item and BT-DMEM + UT-Test item groups, respectively at 10 µg/mL compared to the untreated group. The percent of bone mineralization was distinctly increased by 11.51%, 109.53%, and 83.73% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 100 µg/mL, compared to the UT-DMEM + UT-Test item group. Overall, the Biofield Energy Treated vitamin D3 was significantly improved the bone health parameters and it could be a powerful alternative nutraceutical supplement to combat vitamin D3 deficiency and fight against various bone related problems including rickets, osteomalacia, osteoporosis, osteogenesis imperfecta, Paget’s disease of bone, bone and joint pain, low bone density, bone fractures, deformed bones, osteoma, chondrodystrophia fetalis, stress management and prevention, autoimmune and inflammatory diseases, and anti-aging by improving overall health.
... Collagen is comprised of about 25% to 35% of the total body proteins, mainly distributed in the extracellular matrix compartment. Some factors such as aging and a poor diet can affect the level of collagen in the body [44]. Because, in aged peoples the intake of food nutrition are not adequate as per recommended in terms of energy. ...
The main aim of this experiment was to assess the impact of Consciousness Energy Healing-based vitamin D3 and DMEM medium on bone health parameters. The test items, were divided into two parts. One part of each sample received the Consciousness Energy Healing Treatment by Brian Anthony Weekes and those samples were labeled as the Biofield Energy Treated (BT) samples, while the other parts of each sample were denoted as the untreated test items (UT). Different parameters like ALP, collagen, and bone mineralization were performed to evaluate the bone strength and integrity in human bone osteosarcoma cells (MG-63). The test samples were found as safe in the tested concentrations by MTT cell viability assay. ALP was significantly increased by 19.49% and 63.49% in the UT-DMEM + BT-Test item and BT-DMEM + BT-Test item groups, respectively at 1 µg/mL compared to the UT-DMEM + UT-Test item group. Further, the ALP level was significantly elevated by 35.92% and 61.17% in the UT-DMEM + BT-Test item and BT-DMEM + BT-Test item groups, respectively at 10 µg/mL compared to the UT-DMEM + UT-Test item group. Collagen was significantly increased by 53.75% and 42.43% in the UT-DMEM + BT-Test item and BT-DMEM + UT-Test item groups, respectively at 1 µg/mL compared to the untreated group. Further, the collagen level was significantly increased by 46.54% and 122.61% at 50 and 100 µg/mL, respectively in the BT-DMEM + UT-Test item group compared to the untreated group. Additionally, the percent of bone mineralization was distinctly increased by 18.12%, 96.33%, and 150.85% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 10 µg/mL compared to the untreated group. Further, the percentage of bone mineralization was significantly increased by 61.96 and 22.84% in the BT-DMEM + UT-Test item and BT-DMEM + BT-Test item groups, respectively at 100 µg/mL compared to the untreated group. Overall, the Biofield Energy Treated vitamin D3 was significantly improved the bone health parameters and it could be an alternative nutraceutical supplement to combat vitamin D3 deficiency and fight against various bone related problems including rickets, low bone density, osteomalacia, bone and joint pain, bone fractures, osteoporosis, osteoma, osteogenesis imperfecta, Paget’s disease of bone, deformed bones, chondrodystrophia fetalis, stress management and prevention, autoimmune and inflammatory diseases, and anti-aging by improving overall health.
... Type 1 collagen is the most abundant fibers in all the connective tissue. It is contains approximately 25% to 35% of the total body proteins of extracellular matrix compartment [44]. A lot of literatures reported that supplementation of collagen peptides enhanced bone density, skin elasticity, and reduced the severity of bone-related disorders [45]. ...
The study was aimed to evaluate the effect of Consciousness Energy Healing-based vitamin D3 and DMEM medium on bone health parameters such as alkaline phosphatase (ALP), collagen, and bone mineralization in human bone osteosarcoma cells (MG-63). The test items (vitamin D3 and DMEM), were divided into two parts. One part of each sample was received the Biofield Energy Treatment by Dimitrius Anagnos and those samples were denoted as the Biofield Energy Treated (BT) samples, while the other parts of each sample were referred as the untreated test items (UT). The test samples were found as safe in the tested concentrations by MTT cell viability assay. The level of ALP was significantly increased by 74.86% in the BT-DMEM + BT-Test item and 40.17% in the UT-DMEM + BT-Test item group at 0.1 and 50 µg/mL, respectively compared to the UT-DMEM + UT-Test item group. Moreover, collagen level was significantly increased by 228.22%, 185.40%, and 256.69% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 0.1 µg/mL compared to the UT-DMEM + UT-Test item group. Further, the collagen level was significantly increased by 88.61% and 130.65% in the BT-DMEM + UT-Test item and BT-DMEM + BT-Test item groups, respectively at 1 µg/mL compared to the untreated group. Apart from this, the percent of bone mineralization was distinctly enhanced by 98.61%, 111.67%, and 68.26% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 0.1 µg/mL compared to the untreated group. Additionally, the percentage of bone mineralization was significantly increased by 83.3%, 99.52%, and 50.26% in the UT-DMEM + BT-Test item, BT-DMEM + UT-Test item, and BT-DMEM + BT-Test item groups, respectively at 1 µg/mL compared to the untreated group. Altogether, the Biofield Energy Treated vitamin D3 was significantly improved the bone health parameters and it could be an alternative approach for nutraceutical supplement to combat vitamin D3 deficiency and able to fight against various bone-related disorders including rickets, low bone density, osteomalacia, bone and joint pain, bone fractures, osteoporosis, osteoma, osteogenesis imperfecta, Paget’s disease, deformed bones, chondrodystrophia fetalis, stress management and prevention, autoimmune and inflammatory diseases, and anti-aging by improving overall health.
... This finding is consistent with previous studies that have demonstrated that the long-term effect of SM exposure causes an increase in the rate of osteopenia and osteoporosis (40). Osteoporosis is one of the most common causes of corticosteroid therapy that increases osteoblastic suppression and bone resorption (41), as well as loss of bone collagen that occurs in osteoporosis (42). In addition, Sorva et al. demonstrated that inhaled corticosteroids decreased carboxy propeptide of type I procollagen which is a marker of bone formation (43). ...
Objectives:
This study aims to evaluate combined proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS) metabolic profiling approaches, for discriminating between mustard airway diseases (MADs) and healthy controls and for providing biochemical information on this disease.
Materials and methods:
In the present study, analysis of serum samples collected from 17 MAD subjects and 12 healthy controls was performed using NMR. Of these subjects, 14 (8 patients and 6 controls) were analyzed by GC-MS. Then, their spectral profiles were subjected to principal component analysis (PCA) and orthogonal partial least squares regression discriminant analysis (OPLS-DA).
Results:
A panel of twenty eight metabolite biomarkers was generated for MADs, sixteen NMR-derived metabolites (3-methyl-2-oxovaleric acid, 3-hydroxyisobutyrate, lactic acid, lysine, glutamic acid, proline, hydroxyproline, dimethylamine, creatine, citrulline, choline, acetic acid, acetoacetate, cholesterol, alanine, and lipid (mainly VLDL)) and twelve GC-MS-derived metabolites (threonine, phenylalanine, citric acid, myristic acid, pentadecanoic acid, tyrosine, arachidonic acid, lactic acid, propionic acid, 3-hydroxybutyric acid, linoleic acid, and oleic acid). This composite biomarker panel could effectively discriminate MAD subjects from healthy controls, achieving an area under receiver operating characteristic curve (AUC) values of 1 and 0.79 for NMR and GC-MS, respectively.
Conclusion:
In the present study, a robust panel of twenty-eight biomarkers for detecting MADs was established. This panel is involved in three metabolic pathways including aminoacyl-tRNA biosynthesis, arginine, and proline metabolism, and synthesis and degradation of ketone bodies, and could differentiate MAD subjects from healthy controls with a higher accuracy.
... In general, disruption in bone micro-architecture features leads to reduction in bone mineral density relative to normal healthy bone. Osteoporotic bone exhibits reduced collagen, and consequently results in loss of protein which leads to weakening of bone [12]. Thus, osteoporotic bone is very susceptible to fracture due to increased fragility [6,13]. ...
Bisphosphonates have found application in the treatment of reoccurrence of bone diseases, breast cancer, etc. They have also been found to exhibit antimicrobial, anticancer and antimalarial activities. However, they suffer from pharmacological deficiencies such as toxicity, poor bioavailability and low intestinal adsorption. These shortcomings have resulted in several researchers developing delivery systems that can enhance their overall therapeutic effectiveness. This review provides a detailed overview of the published studies on delivery systems designed for the delivery of bisphosphonates and the corresponding in vitro/in vivo results.
... Osteoporosis is the result of progressive catabolic changes, and it is generally accepted that the risk for osteoporosis increases with age (85,107). Changes found in skin collagen also occur in bone collagen with aging and may be a causal counterpart to loss of bone quality in senile osteoporosis (116). In addition, age-related changes of noncalcified collagen in human cortical bone have been reported (132). ...
Until recently, age, particularly old age, was considered a contraindication to the placement of dental implants. However, this was based largely on anecdotal dogma rather than on empirical information. This review considers the biological, clinical and socio-economic implications of implants placed in the aged population. Aging has been shown to have an influence on the biological aspects of soft- and hard-tissue wound healing and tissue remodeling, which may influence the establishment and maintenance of implant integration. However, information to date indicates that age should not be an a priori contraindication for implant placement and there is good evidence to indicate that dental implants can be placed successfully in the elderly with good clinical and socio-economic outcomes.
... 9,11 A reduction in the amount of collagen in the skin of about 1% per year after 21 years of age is described, resulting in thickness reduction and elasticity loss, which is directly related to the wrinkles depth. 11,12 Changes occurring after menopause are even more striking, including loss of about 30% of skin collagen in the first 5 years and annual loss of 0.55% of elastin. 13,14 The biosynthesis process of collagen after the third or fourth decade of life remains at a low level, insufficient to allow mature skin to repair or replace the collagen that has been lost as part of the degradation processes associated with age. ...
Silicon is the second most abundant element on Earth, and the third most abundant trace element in human body. It is present in water, plant and animal sources. On the skin, it is suggested that silicon is important for optimal collagen synthesis and activation of hydroxylating enzymes, improving skin strength and elasticity. Regarding hair benefits, it was suggested that a higher silicon content in the hair results in a lower rate of hair loss and increased brightness. For these beneficial effects, there is growing interest in scientific studies evaluating the efficacy and safety of using dietary supplements containing silicon. Its use aims at increasing blood levels of this element and improving the skin and its annexes appearance. There are different forms of silicon supplements available and the most important consideration to be made in order to select the best option is related to safety and bioavailability. Silicon supplements are widely used, though there is wide variation in silicon bioavailability, ranging from values below 1% up to values close to 50%, depending on the chemical form. Therefore, the aim of this study was to evaluate the scientific literature related to the different chemical forms of silicon supplements available and the limitations and recent progress in this field. According to reported studies, among the different chemical forms available, the orthosilicic acid (OSA) presents the higher bioavailability, whereas the others forms have absorption inversely proportional to the degree of polymerization. However, clinical studies evaluating safety and efficacy are still lacking.
... This result is consistent with previous studies that reported exposure to SM clearly increases the rate of osteopenia and osteoporosis and also causes the corneal collagen degradation (Agin et al., 2004, Naderi et al., 2010. It is well known that loss of bone collagen occurs in osteoporosis (Shuster, 2005). Agin and et al. evaluated the rate of osteoporosis in asthmatic patients compared to SM-induced patients who were receiving corticosteroids as the treatment for chronic pulmonary complications and observed that SM clearly increases the rate of osteoporosis (Agin et al., 2004). ...
Sulfur mustard (SM) is a vesication chemical warfare agent for which there is currently no antidote. Despite years of research, there is no common consensus about the pathophysiological basis of chronic pulmonary disease caused by this chemical warfare agent. In this study, we combined chemometric techniques with nuclear magnetic resonance (NMR) spectroscopy to explore the metabolic profile of sera from SM-exposed patients. A total of 29 serum samples obtained from 17 SM-injured patients, and 12 healthy controls were analyzed by Random Forest. Increased concentrations of seven amino acids, glycerol, dimethylamine, ketone bodies, lactate, acetate, Citrulline, and creatine together with the decreased very low-density lipoproteins (VLDL) levels were observed in patients compared with control subjects. Our study reveals the metabolic profile of sera from SM-injured patients and indicates that NMR-based methods can distinguish these patients from healthy controls.
... Collagen is a structural protein that plays a crucial role in the formation and maintenance of the extracellular matrix of connective tissue and represents one third of the total protein in humans (150). Collagen, like most biological molecules, accumulates damage as an organism ages which can result in tissue damage and diseases such as osteoporosis (150,191). Moreover, collagen expression declines with age (220). ...
The ability to respond to hostile environmental conditions is critical for the survival of an organism. Oxidative stress is an adverse state in which reactive oxygen species (ROS) accumulate to a harmful level and, if left unresolved, can lead to cellular dysfunction and organismal disease. Sophisticated detoxification systems, characterized by a battery of enzymatic antioxidants, are utilized to neutralize ROS thereby reducing stress. However, ROS are also purposefully produced by designated cellular enzymes to facilitate the signaling and regulation of critical physiological processes. Therefore, both the production and neutralization of ROS must be tightly controlled. Indeed, the expression of detoxification enzymes is regulated by major oxidative stress response transcription factors, such as Nrf2 and SKN-1 in mammals and the model organism Caenorhabditis elegans, respectively. The activity of both Nrf2 and SKN-1 is highly regulated and many conserved mechanisms are used to facilitate proper control of these two transcription factors, making C. elegans a powerful tool in which to study the complex regulation of the major oxidative stress response transcription factors.
Herein, we uncover a novel mechanism of SKN-1 regulation, in which a thioredoxin, TRX-1, negatively impacts the intestinal subcellular localization of this transcription factor in a cell non-autonomous manner from the ASJ neurons. This function of TRX-1 is specific, as SKN-1 regulation is not a common role for other C. elegans thioredoxins. Moreover, SKN-1 regulation is a redox-independent function of TRX-1 and does not impact transcriptional activation or previously characterized SKN-1-dependent protective responses, such as the oxidative or pathogen stress responses. Thioredoxins are understudied in C. elegans, but play an important role in worm lifespan. RNA Seq was used as an unbiased approach to determine potential physiological role(s) of TRX-1. Uncovered associations include changes in the expression of genes involved in collagen biosynthesis and lipid metabolism. In summary, TRX-1 regulates SKN-1 in a manner which dissects subcellular localization and transcriptional activation, emphasizing the importance of strict regulation of SKN-1 activation.
... Abnormalities of type I and V collagen fibers may cause skeletal fragility by irregular arrangement of hydroxyapatite crystals and non mineralized collagen fibrils [7]. As a matter of fact, it has been suggested that adequate quality collagen is required to form normally mineralized bone [8,9]. ...
Previous studies have reported an increased prevalence of osteoporosis in Ehlers-Danlos syndrome (EDS), but these were limited by a small number of patients and lack of information on fragility fractures. In this crosssectional study, we evaluated the prevalence of radiological vertebral fractures (by quantitative morphometry) and bone mineral density (BMD, at lumbar spine, total hip and femoral neck by dual-energy X-ray absorptiometry) in 52 consecutive patientswith EDS (10 males, 42 females; median age 41 years, range: 21-71; 12with EDS classic type, 37 with EDS hypermobility type, 1 with classic vascular-like EDS, and 2 without specific classification) and 197 control subjects (163 females and 34 males; median age 49 years, range: 26-83) attending an outpatient bone clinic. EDS patients were also evaluated for back pain by numeric pain rating scale (NRS- 11).Vertebral fractures were significantly more prevalent in EDS as compared to the control subjects (38.5% vs. 5.1%; p < 0.001) without significant differences in BMD at either skeletal sites. In EDS patients, the prevalence of vertebral fractures was not significantly (p = 0.72) different between classic and hypermobility types. BMD was not significantly different between fractured and non-fractured EDS patients either at lumbar spine (p = 0.14), total hip (p=0.08), or femoral neck (p=0.21). Severe back pain(≥7 NRS)was more frequent in EDS patientswith vertebral fractures as compared to thosewithout fractures (60% vs. 28%; p=0.04). Inconclusion, this is the first study showing high prevalence of vertebral fractures in a relatively large population of EDS patients. Vertebral fractures were associated with more severe back pain suggesting a potential involvement of skeletal fragility in determining poor quality of life. The lack of correlation between vertebral fractures and BMD is consistent with the hypothesis that bone quality may be impaired in EDS.
... One explanation for these observations may be those osteoblasts undergoing apoptosis release ALP into the blood [43,44]. Osteoporosis is also associated with bone collagen loss [45]. PICP, a marker of collagen synthesis, is released during the synthesis of osteocalcin and type I collagen [46]. ...
Mushrooms are the best nonanimal food source of vitamin D2. Pulsed irradiation can enhance vitamin D2 in mushrooms quickly. We investigated the effect of supplementing high vitamin D2Pleurotus ferulae mushrooms in a mouse model of osteoporosis. Thirty-two female C57BL/6JNarl mice were divided into four groups including sham, ovariectomized (OVX), OVX+nonpulsed mushroom (NPM) and OVX+pulsed mushroom (PM). After 23weeks of treatment, serum samples were analyzed for osteoblast and osteoclast indicators, as well as metabolites using NMR spectroscopy. To examine bone density, femurs were analyzed using micro-computed tomography. The NPM and PM treatment mice showed increased bone density in comparison with OVX mice. In addition, the PM mice showed higher osteoblast and lower osteoclast indicators in comparison with OVX mice. Serum metabolomics analysis indicated several metabolites that were different in PM mice, some of which could be correlated with bone health. Taken together, these results suggest that pulsed irradiated mushrooms are able to increase bone density in osteoporotic mice possibly through enhanced bone metabolism. Further studies in humans are needed to show their efficacy in preventing osteoporosis.
Copyright © 2015. Published by Elsevier Inc.
... Despite such differences, the effects of resistance exercise on murine bone may also be relevant for human studies. These authors' findings are important since a reduction in bone collagen content has been suggested to take part in bone loss in diabetes, osteoporosis and aging 34,[45][46][47] . It is also clinically relevant, especially for men, given that in at present around onethird of hip fractures occur in men, and the mortality rate one year after hip fracture is higher than in women 2 . ...
... Therefore, a lower value of z and a higher resonance frequency found in the patients with osteoporosis with and without fracture compared with healthy adults implies lower viscous damping properties of the bone among the patient groups. Such a finding is consistent with a recent report of collagen loss as a contributing factor in decreased viscoelastic properties of bones and potential association of osteoporosis with pathogenesis (41,42). Previous studies with bone turnover markers have also suggested that bone matrix component type I collagen level is a contributing factor in determining damping/viscoelastic capacity of bone (41e44). ...
We describe a novel approach to characterize bone quality noninvasively, a measurement that quantifies aggregate shock-absorption capacity of load-bearing bones as a measure of mechanical structural integrity during exposure to real-time self-induced in vivo loading associated with heel strike. The outcome measure, damping factor, was estimated at 5 load-bearing anatomical sites: ankle, tibial tuberosity, femoral condyle, lower back (at 3rd lumbar vertebra), and upper back (7th thoracic vertebra) plus the forehead in 67 patients with postmenopausal osteoporosis with and without documented vertebral fractures. The damping value was significantly lower in patients with ver-tebral fractures compared with those without a fracture (range: À36% to À72%; median: À44%). In these women with osteoporosis, damping factor was able to discriminate between patients with and without vertebral fractures, whereas traditional measures of bone density and biomechanical measures obtained from bone geometry were not significantly different between the groups.
... Collagen is found in many tissues and organs, such as veins, arteries, skin, tendons, vascular, ligaments, bone, cartilage, and the extracellular matrix, where it has many roles in host defense [1][2][3][4]. This suggests that any loss of collagen functionality or stability can have serious repercussions for the human body in diseases, such as Osteogenesis imperfecta, Ehlers-Danlos syndrome, infantile cortical hyperostosis, and collagenopathy [5][6][7][8][9][10][11][12]. Thus, it is important to understand that any changes in the classical structure of collagen can generate a cascade effect involving several tissues and organs. ...
Collagen is the most abundant protein in the whole human body and its instability is involved in many important diseases, such as Osteogenesis imperfecta, Ehlers-Danlos syndrome, and collagenopathy. The stability of the collagen triple helix is strictly related to its amino acid sequence, especially the main Gly-X-Y motif. Many groups have used computational methods to investigate collagen's structure and the relationship between its stability and structure. In this study, we initially reviewed the most important computational methods that have been applied in this field. We then assembled data on a large number of collagen-like peptides to build the first Markov chain model for predicting the stability of the collagen at different temperatures, simply by analyzing the amino acid sequence. We used the literature to assemble a set of 102 peptides and their relative melting temperatures were determined experimentally, indicating a great variance with the main motif of the collagen. This dataset was then split in two classes, stable and unstable, according to their melting temperatures and the dataset was then used to build artificial neural network (ANN) models to predict collagen stability. We built models to predict stability at temperatures of 38°C, 35°C, 30°C, and 25°C degrees, and all models had an accuracy between 82% and 92%. Several cross-validation procedures were performed to validate the model. This method facilitates fast and accurate predictions of collagen stability at different temperatures.
Objectives
Silicium (silicon), an essential trace element, plays a critical role in maintaining skin health, including collagen synthesis, hydration, and elasticity. Mesoporosil®, a novel bioavailable form of silicium, offers a promising solution for enhancing skin properties. This study evaluates the efficacy and safety of Mesoporosil® in improving skin firmness, hydration, and elasticity in women with aging skin.
Materials and Methods
This 84-day interventional study involved 22 female volunteers aged 40–66 years with moderate to severe facial aging and dry skin. Participants consumed one daily tablet of Mesoporosil® containing 14 mg of silicon. Assessments were conducted at baseline, day 28, day 56, and day 84. Primary outcomes included subjective improvements in skin firmness, hydration, elasticity, and radiance, assessed through a detailed 24-item questionnaire.
Results
All 22 participants completed the study without dropouts. Subjective assessments showed progressive improvements in skin parameters over the treatment period. Significant acceptance was observed on day 28 (55.8%), day 56 (62.7%), and day 84 (61.4%). Three sensory experience parameters – ease of oral intake, absence of aftertaste, and lack of gastric distress – met the 80% satisfaction threshold consistently. Skin firmness, hydration, wrinkle reduction, radiance, and elasticity showed cumulative enhancement over the 12 weeks. No adverse events or discomforts were reported, indicating excellent tolerance and safety of the supplement.
Conclusion
Mesoporosil® demonstrated significant efficacy in enhancing skin firmness, hydration, and elasticity, with high levels of participant satisfaction and excellent safety. These findings support the potential of Mesoporosil® as an effective supplement for promoting healthy aging in women with aging skin.
The proof of principle of the therapeutic potential of heat shock protein 47 (HSP47) for diseases characterized by defects in collagen I synthesis is here demonstrated in osteogenesis imperfecta (OI), a prototype of collagen disorders. Most of the OI mutations delay collagen I chain folding, increasing their exposure to posttranslational modifications that affect collagen secretion and impact extracellular matrix fibril assembly. As a model, we used primary fibroblasts from OI individuals with a defect in the collagen prolyl 3-hydroxylation complex, since they are characterized by the synthesis of homogeneously overmodified collagen molecules. We demonstrated that exogenous recombinant HSP47 (rHSP47) is taken up by the cells and localizes at the ER exit sites and ER-Golgi intermediate compartment. rHSP47 treatment increased collagen secretion, reduced collagen posttranslational modifications and intracellular collagen retention, and ameliorated general ER proteostasis, leading to improved cellular homeostasis and vitality. These positive changes were also mirrored by an increased collagen content in the OI matrix. A mutation-dependent effect was found in fibroblasts from 3 probands with collagen I mutations, for which rHSP47 was effective only in cells with the most N-terminal defect. A beneficial effect on bone mineralization was demonstrated in vivo in the zebrafish p3h1-/- OI model.
Collagen, the predominant protein in mammals, serves as an essential structural component in various connective tissues such as skin, bones, tendons and ligaments. It imparts mechanical strength and structural integrity, crucial for supporting and protecting softer tissues and internal organs. Displaying significant heterogeneity, collagen encompasses 29 identified types, which form both fibrillar and non-fibrillar structures. Fibrillar collagens, such as types I, II, and III, are vital for connective tissue stability, while non-fibrillar collagens, including types IX and XVIII, fulfill specialized roles in anchoring and network formation. Collagen interacts with diverse receptors, including integrins, discoidin domain receptors (DDRs), glycoprotein VI (GPVI), and leukocyte-associated IG-like receptor-1 (LAIR-1), which are integral in regulating essential physiological processes such as cell adhesion, migration, and tissue remodeling. Mutations in collagen genes are associated with a range of disorders, including osteogenesis imperfecta (OI), Type II collagenopathies, Ehlers-Danlos Syndrome type IV, and Alport syndrome. Therefore, deepening our comprehension of collagen’s structural diversity and its biological interactions is imperative for elucidating its multifaceted roles and implications in pathology.
In this chapter, we aim to summarize the recent advancements in developing collagen-based nanoparticles as drug carriers and their biomedical applications. A paradigm shift has taken place in the field of nanotechnology due to the use of protein-based drug delivery systems. Collagen is the most abundant protein and the primary structural component of connective tissues in the body is being assessed for its unique properties like biocompatibility, biodegradability, low antigenicity, and ease of fabrication of nanoparticles making it the most cost-effective protein-polymer available for drug delivery. The structural elucidation of the collagen molecule has fundamentally formed the basis for its unique physicochemical properties and stability of the molecule. Significant research has suggested no toxicity issues associated with the delivery of collagen-based nanoparticles. In addition, various fabrication techniques for collagen-based nanoparticles are also discussed in the chapter.
Micro greens are leafy green vegetables which are harvested just after the germination of seeds and are fully developed cotyledon leaves along with one pair of very small partially developed true leaves. These are also called as "vegetable confetti". It is known for high nutrient contents and calories produced from seeds of various kinds of herbs, vegetables and other plants. Seeds of green leafy vegetables, salad greens, herbs, seeds of plants having edible flowers can be used for raising micro greens. In this study fenugreek, mustard and coriander seeds were taken to produce micro greens. The macro and micro nutrients were analysed and it was found that micro greens have high nutritional value in comparison to mature vegetables and sprout seeds. The nutrient levels varied with variation in growing medium, both hydroponically and in different soil condition and also the time of harvesting. The cultivation and consumption of micro greens at home will not only provide nutrition but also will ensure good health because of organic origin. Keeping in view with the progressive growth of human population, micro greens production will not require much land areas and any one can grow it within home with little open space like terrace or balcony and can transform the home in to a year round vegetable garden.
Background:
fractures occur more commonly in the thoracic than in the lumbar spine. Physical activity complemented with pharmacological interventions has been advocated as a preventive measure for osteoporosis. However, walking has been shown to produce only a small improvement in spinal bone mineral density. The characteristics of vibration transmission during walking at the lumbar and thoracic spines may be different, and this may help explain the relative incidence of fractures in the two spine regions.
Objective:
to determine how mechanical vibration is transmitted in the lumbar and thoracic spines in older adults with and without osteoporosis.
Methods:
16 young healthy adults, 19 older adults without osteoporosis and 41 adults with osteoporosis were recruited. Inertial sensors were attached to the skin over the lumbar and thoracic spines for recording the vibration transmitted during level walking. Vibration characteristics were compared across lumbar and thoracic spines and across groups.
Results:
the lumbar spine generally amplified the vibration transmitted during walking, whereas the thoracic spine exhibited a much smaller amplification effect, except at the lowest frequency. The magnitude of vibration was generally reduced in the older spines. Osteoporosis had minimal effects on vibration transmission.
Conclusions:
the larger amplification of vibration in the lumbar spine may explain the lower incidence of vertebral fractures in this region when compared to the thoracic spine. Ageing alters the transmission of vibration in the spine while osteoporosis has minimal effects. Future research should determine the characteristics of vibration transmitted through the thoracic spine during other physical activities.
Background: Senile purpura is characterized by ecchymoses on the extensor surfaces of the forearms and the dorsa of hands in the elderly. The prevalence is around 10% in the eight and ninth decades. Its occurrence is secondary to the fragility of blood vessel walls caused by atrophy of dermal collagen bundles and solar elastosis due to intrinsic aging and photoaging. For prevention of senile purpura, sunscreens and barrier protection should be used. However, there has been no specific medical treatments developed for senile purpura. Objective: The purpose of this study was to evaluate the clinical efficacy of a topical calcineurin inhibitor for the treatment of senile purpura. Methods: Seven patients with senile purpura applied 1% pimecrolimus cream twice daily for 2 weeks. Efficacy was evaluated by the subject's assessment and by the objective findings using photographic assessment. Results: There was an 8.5% reduction in the purpuric area compared with the initial lesion. When the Wilcoxon signed-rank test was used for determination of the purpuric area between the pre-treatment condition and the post-treatment condition, the therapeutic effect was statistically significant (p=0.004). Three of seven patients (42.9%) were satisfied with their treatment, and four of them (57.1%) were neither satisfied nor dissatisfied. No adverse events were observed during the treatment and follow up periods. Conclusion: This study shows that 1% pimecrolimus cream can be an effective and safe treatment modality for senile purpura.
The maintenance of skin function and appearance is important and plays an influential role in the quality of life for women who can spend up to one-third of their lives in a hypoestrogenic state. Ideally, a safe and effective topical hormone replacement preparation without systemic adverse effects would be a highly desirable treatment for hypoestrogenic skin. Menopausal skin effects occur within the overall background of progressive inexorable intrinsic alterations that are superimposed changes over extrinsic changes, principally due to cumulative ultraviolet exposure. The principal way to discern skin alterations related to hypoestrogenemia occurring in menopausal women is through study of the amelioration that occurs after estrogen-based hormonal replacement. Dry skin complaints are common and generally can easily be treated with small alterations in personal lifestyle habits. Significant menopausal-associated sweating can be managed with estrogen-based hormone replacement therapy (HRT) or other systemic therapies. HRT helps to maintain or restore collagen and skin thickness, possibly dampening of the pace of development of fine wrinkles, increasing skin strength, improving acute wound healing rates, and perhaps preventing skin breakdown in elderly postmenopausal women.
We evaluated functional measures of neuromuscular integrity and bone's resistance to fracture as a combined tool in discriminating osteoporosis patients with and without fractures. Functional aspects of neuromuscular integrity were quantified with a noninvasive measure of static and dynamic functional postural stability (FPS), and fracture resistance was obtained with bone shock absorption in patients with osteoporosis aged 65-85 and compared our measures with dual-energy X-ray absorptiometry and Fracture Risk Assessment Tool (FRAX [World Health Organization Collaborating Center for Metabolic Bone Diseases, Sheffield, UK]) in women with osteoporosis, some with and some without vertebral fractures. Patients with vertebral fracture showed larger static FPS (postural sway excursion) in the mediolateral and anterior-posterior directions, suggesting poorer balance. Most of the variables of dynamic FPS showed significant differences between fracture and no-fracture groups (e.g., the fracture group took significantly longer during turning, implying poorer dynamic balance control). Also, compared with healthy control subjects, all 4 dynamic FPS responses for osteoporosis patients with and without fracture were significantly poorer, suggesting potential risk for falls. In summary, patients with osteoporosis who have vertebral fractures (compared with patients with similarly low bone mineral density and other nonfracture risk fractures) have not only lower bone shock absorption damping (ζ) but also increased postural imbalance.
Copyright © 2015 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.
The nanoscale structural order of air-dried rat-tail tendon is investigated using small-angle X-ray scattering (SAXS). SAXS fiber diffraction patterns were collected with a superbright laboratory microsource at XMI-LAB [Altamura, Lassandro, Vittoria, De Caro, Siliqi, Ladisa & Giannini (2012). J. Appl. Cryst.45, 869–873] for increasing integration times (up to 10 h) and a novel algorithm was used to estimate and subtract background, and to deconvolve the beam-divergence effects. Once the algorithm is applied, the peak visibility improves considerably and reciprocal space information up to the 22nd diffraction order is retrieved (q = 0.21 Å⁻¹, d = 29 Å) for an 8–10 h integration time. The gain in the visibility is already significant for patterns collected for 0.5 h, at least on the more intense peaks. This demonstrates the viability of detecting structural changes on a molecular/nanoscale level in tissues with state-of-the-art laboratory sources and also the technical feasibility to adopt SAXS fiber diffraction as a future potential clinical indicator for disease.
Surgical site infection in the spine is a serious postoperative complication. Factors such as posterior surgical approach, arthrodesis, use of spinal instrumentation, age, obesity, diabetes, tobacco use, operating-room environment, and estimated blood loss are well established in the literature to affect the risk of infection. The goal of this study was to analyze and identify independent risk factors for surgical site infection among spine patients undergoing posterior lumbar instrumented arthrodesis.
The medical records of 3218 patients who underwent posterior lumbar instrumented arthrodesis from January 2000 to December 2006 were reviewed to identify those who developed a postoperative infection (eighty-four patients; 2.6%). The size of this single-institution patient group allowed construction of a multivariate logistic regression model to evaluate the independent associations of potential risk factors for surgical site infection in the spine.
In the final regression model, obesity, estimated intraoperative blood loss, ten or more people in the operating room, a dural tear, history of diabetes, chronic obstructive pulmonary disease, coronary heart disease, and osteoporosis were critical risk factors for the onset of spinal surgical site infection. Obesity and a history of chronic obstructive pulmonary disease were the strongest risk factors for postoperative spinal infection after adjusting for all other variables. The most common pathogen was methicillin-resistant Staphylococcus aureus with a prevalence of 34.5%. This study established a single institution infection rate for posterior lumbar instrumented arthrodesis at 2.6%.
This analysis confirms previously demonstrated risk factors for postoperative infection while reporting on new potential independent risk factors of osteoporosis, chronic obstructive pulmonary disease, and dural tears in the setting of posterior lumbar instrumented arthrodesis. Areas of new research can focus on the roles these novel factors may play in the pathogenesis of surgical site infections in the spine.
Skin aging has received tremendous attention in recent years by both scientists and the lay public. This article reviews the evidence that homocysteine, an intermediary sulfhydryl-containing amino acid implicated in atherosclerosis, can accelerate skin aging and the aging of internal organs (universal aging).
Tenascin-X (TNX) is an extracellular matrix (ECM) glycoprotein, the absence of which in humans leads to a recessive form of Ehlers-Danlos syndrome (EDS), a group of inherited connective tissue disorders characterized by joint hypermobility, skin hyperextensibility, and tissue fragility. A mouse model of TNX-deficient type EDS has been used to characterize the dermatological, orthopedic, and obstetrical features. The growing insight in the clinical overlap between myopathies and inherited connective tissue disorders asks for a study of the muscular characteristics of inherited connective tissue diseases. Therefore, this study aims to define the muscular phenotype of TNX knockout (KO) mice.
We performed a comprehensive study on the muscular phenotype of these TNX KO mice, consisting of standardized clinical assessment, muscle histology, and gene expression profiling of muscle tissue. Furthermore, peripheral nerve composition was studied by histology and electron microscopy.
The main findings are the presence of mild muscle weakness, mild myopathic features on histology, and functional upregulation of genes encoding proteins involved in ECM degradation and synthesis. Additionally, sciatic nerve samples showed mildly reduced collagen fibril density of endoneurium.
The muscular phenotype of TNX KO mice consists of mild muscle weakness with histological signs of myopathy and of increased turnover of the ECM in muscle. Furthermore, mildly reduced diameter of myelinated fibers and reduction of collagen fibril density of endoneurium may correspond with polyneuropathy in TNX-deficient EDS patients. This comprehensive assessment can serve as a starting point for further investigations on neuromuscular function in TNX KO mice.
IT is a common observation that exposed skin ``ages'' more rapidly than skin covered by clothing, and we have shown that this is associated with a decrease in the total collagen content of exposed skin1. One of the features of ageing collagen is its decreased solubility, and we were able to show that when the skin from hairless mice is exposed to ultra-violet radiation in vitro there is a decrease in the soluble collagen fractions2 together with an increase in intermolecular cross linkage3 similar to that which occurs in ageing skin. The question therefore arose as to whether ultra-violet radiation would produce this effect in the intact living animal.
Skin collagen has been measured in a normal population, in patients treated with corticosteroids for rheumatoid arthritis, and in patients with rheumatoid arthritis who had not received corticosteroids. Total skin collagen is greater in men than in women and it decreases with increasing age in both sexes. The skin collagen content of the patients with rheumatoid arthritis who had not been treated with corticosteroids was lower than in the normal population but this difference was of low significance. Total skin collagen content is considerably less than normal in patients treated with corticosteroids and this decrease is related to the total dose of corticosteroid. This explains the thin skin, prominent small vessels, purpura, and striæ of spontaneous and iatrogenic Cushing's syndrome.
Total skin collagen is greatly increased in women with hirsuties. This is presumably due to androgen, whether locally produced or circulating.
The thickness and collagen content of forearm skin were measured in 13 patients with systemic sclerosis, in 8 of whom the forearm skin was found to be clinically affected by the disease. No increase in skin thickness or its collagen content was found. The thickness and collagen content of the clinically affected forearm skin were usually decreased and collagen density was normal. It is concluded that the clinical impression of thickness and toughness is due to binding down of the skin to deeper structures. The similarity of atrophic morphoea and systemic sclerosis is discussed.
Striae are always initiated by stretch whether the stretch is excessive or minimal: spontaneous striae do not occur. Cross-linkage of collagen appears to be more important than amount of collagen in permitting striae in response to stretch. An increase in cross linkage as in age increases the resistance to stretch deformation, but this rigidity leads ultimately to tearing of the skin and not striae. At the other extreme, the absence of crosslinkage leads to "elasticity" and excessive stretching with eventual rupture of the skin if the stretch goes beyond the elastic limit, but again, no striae. Striae appear to occur therefore only in skin in which the rigid cross-linked collagen and "elastic" unlinked collagen thus permitting a limited degree of stretch and a limited intradermal rupture, i.e. striae. (Although rigidity and elasticity are presented here in terms of collagen cross-linkage it seems probable that changes in interfibrillary materials such as glycosaminoglycans will prove important in this respect). This balance of stretch and limited tear is a continuous process and is an adaptation to the needs of growth in adolescence and change in body mass in early adult life and there are many many subclinical "striae" for each gross tear which is recognised clinically. An important factor likewise appears to be rate of stretch since if it is very slow, striae are less likely; there is "give" and new collagen formation. Although this working hypothesis is consonant with the facts only further work will show whether this smooth consonance is that of the fable or the weathered rock of fact.
Forearm skin collagen, dermal thickness and collagen density were measured in a large number of normal subjects as a standard reference for future studies. Skin collagen decreased with age and was less in the females at all ages. There is a direct relationship between skin collagen and dermal thickness but variations in collagen density in disease limit the use of dermal thickness as a guide to changes in its collagen content.
The collagen content of skin as expressed per unit of surface area, is decreased in patients with osteogenesis imperfecta. This indicates a widespread if not generalised defect of connective tissue.
The thickness of the forearm skin and its collagen content and density were measured in a group of patients with acromegaly and hypopituitarism. In acromegaly the total content, thickness and collagen density were all increased. There was a smaller and less consistent increase in percentage collagen content. In hypopituitarism total skin collagen and thickness were both decreased and collagen density and percentage collagen content remained normal.
Six patients with Cushing's Syndrome were studied. Skin collagen was measured as hydroxyproline and expressed per unit surface area and fat free dry weight. Skin thickness was measured radiologically and collagen density calculated. By comparison with a large series of normals it was found that total skin thickness, skin collagen content and probably density were decreased in Cushing's Syndrome.
Total skin collagen was found to be decreased in untreated patients with osteoporosis, particularly women, but increased after treatment with androgens in women. Decreased body collagen may possibly be a primary defect in osteoporosis, while androgens may increase total skin collagen.
Recent experimental work has demonstrated that mutations that alter the synthesis or structure of type I collagen, or of its precursor type I procollagen, are the cause of the brittleness of bones seen in many variants of osteogenesis imperfecta (OI). They also account for the hyperextensibility of skin, tendons, and ligaments seen in some variants of Ehlers-Danlos syndrome (EDS). Many of the recent findings are not particularly surprising. Type I collagen is the principal protein of bone; it accounts for about half of the dry weight of the bone and as much as 85% of the demineralized dry weight of the tissue. Three aspects of recent discoveries, have been surprising. One surprise has been that a mutation that alters the structure of one region of the type I procollagan can produce a disease that primarily affects skin, tendons, and ligaments, whereas a mutation that makes a very similar change in another part of the same molecule produces a disease that primarily affects bone. A second surprise in the recent work on molecular defects in OI and EDS has been the discovery of a phenomenon that can be referred to as 'protein suicide'. One variant of OI is produced by a deletion of about 500 base pairs (bp) in about the middle of one allele for the proα1(I) chain. The deletion leaves coding sequences on either side of the deletion in register. As a result, the allele is expressed and half the proα1 chains synthesized by fibroblasts from the patient are shortened by about 80 amino acids. The other allele for proα1 chains is normal, and half the proα1 chains synthesized are normal. However, because the structure of the proα1(I) chain beyond the deletion is normal, the shortened proα1 chains associate with and become disulfide-linked to normal proα1 and proα2 chains synthesized by the same fibroblasts. Three-fourths of the procollagen trimers synthesized by fibroblasts contain either one or two shortened proα chains. The shortening of the proα1(I) chain in this variant is so great that the presence of even one shortened proα1 chain in this variant is so great that the presence of even one shortened proα1 chain in a procollagen molecule prevents it from folding into a triple-helical conformation. Therefore, trimers containing either one or two shortened proα1 chains cannot be used to form collagen fibers. Instead, they are rapidly degraded. The third surprise from recent work on OI and EDS has been the discovery that mutations that shortened or lengthened the proα chains of type I procollagen are relatively common. Of the first 15 variants of OI we have examined in our own laboratory, three involved synthesis of a shortened proα1 or proα1 chain. Two others may possibly involve synthesis of a lengthened proα1 chain. Byers et al. reported on another variant of OI with a shortened proα2(I) chain and a variant of the Marfan syndrome with a lengthened proα2(I) chain. The reasons for the high frequency of such mutations in procollagen genes is not clear. In the best studied example, a shortened proα1 chain is synthesized because of a partial deletion of the allele. Procollagen genes may be particularly prone to such mutations because the coding sequences are highly repetitive with frequent sequences of -GGN-CCN-CCN- coding for -Gly-Pro-Hyp- in the α-chain domains of the protein. The repetitive DNA sequences may well predispose the genes to unequal cross-over mutations during meiosis.
The features of a 32 year old woman with Ehlers-Danlos syndrome type VIIB and affected members of her family, resulting from a mutation in one COL1A2 allele, were studied. Her dermal type I collagen contained alpha 2(I) chains and mutant pN-alpha 2(I) chains in which the amino-terminal propeptide remained attached to the alpha 2(I) chain. She was heterozygous for an AG-->AC mutation at the splice acceptor site of intron 5 of the COL1A2 gene. The mutation activated a cryptic AG splice acceptor site corresponding to positions +14 and +15 of exon 6 of the COL1A2 gene. In contrast to previous reports only five, rather than all 18, amino acids encoded by exon 6 were deleted in the proband. The deleted peptide removed the amino-proteinase cleavage site, but not the nearby lysine cross linking site in the amino-telopeptide of the alpha 2(I) chain. She was born with bilateral hip dislocations, knee subluxations, and generalised joint hypermobility. Bilateral inguinal herniae and an umbilical hernia were present at birth. Facial features included a depressed nasal bridge with prominent paranasal folds. The skin was soft, moderately hyperelastic, and sagged over the face. Skin fragility and easy bruising were apparent from childhood. Skin wounds healed slowly and with broad, paper thin scars. Throughout her life, she had multiple fractures of the small bones of her hands and feet following moderate trauma. Electron microscopy of the proband's dermis as well as deep fascia and hip joint capsule from her affected brother showed that collagen fibrils in transverse section were nearly circular but with irregular margins. Light microscopy of bone from her affected brother and son showed normal Haversian systems and lamellar bone. All of these tissues contained approximately equal amounts of the normal and mutant alpha2(I) chains. The findings of this study confirm that loss of the amino-proteinase cleavage site of the pro alpha2(I) collagen chains, owing to anomalous splicing of exon 6 sequences in the conversion of pre-mRNA to mRNA, produces the clinical features of Ehlers-Danlos syndrome type VIIB. The history of frequent fractures found in this family is atypical and indicates an overlap with osteogenesis imperfecta.
Osteoporosis occurs commonly in homocystinuria. The underlying pathobiochemical mechanism remains unclear; disturbed cross-linking of collagen has been suggested but this hypothesis has not been fully tested, nor have studies on collagen synthesis been performed. We therefore used recently available noninvasive tests for collagen synthesis and cross-linking to examine 10 patients with homocystinuria. Synthesis of collagen type I and type III was not different from age-matched healthy controls as reflected by comparable plasma levels of carboxyterminal propeptide of type I procollagen (PICP) and of plasma levels of N-terminal propeptide of procollagen type III (PIIINP). Collagen type I cross-links expressed by serum carboxyterminal telopeptide of collagen type I (ICTP) were 1.14 +/- 0.24 micrograms/l in the patient group versus 3.29 +/- 0.32 micrograms/l in the control group. This significant reduction of cross-links in the group with homocystinuria did not correlate with serum homocysteine or homocysteic acid concentrations. Our data clearly indicate that the disturbed cross-linking hypothesis still holds and that the bone manifestations of homocystinuria are not due to deficient collagen synthesis.
There is no one cause of bone fragility; genetic and environmental factors play a part in development of smaller bones, fewer or thinner trabeculae, and thin cortices, all of which result in low peak bone density. Material and structural strength is maintained in early adulthood by remodelling; the focal replacement of old with new bone. However, as age advances less new bone is formed than resorbed in each site remodelled, producing bone loss and structural damage. In women, menopause-related oestrogen deficiency increases remodelling, and at each remodelled site more bone is resorbed and less is formed, accelerating bone loss and causing trabecular thinning and disconnection, cortical thinning and porosity. There is no equivalent midlife event in men, though reduced bone formation and subsequent trabecular and cortical thinning do result in bone loss. Hypogonadism contributes to bone loss in 20-30% of elderly men, and in both sexes hyperparathyroidism secondary to calcium malabsorption increases remodelling, worsening the cortical thinning and porosity and predisposing to hip fractures. Concurrent bone formation on the outer (periosteal) cortical bone surface during ageing partly compensates for bone loss and is greater in men than in women, so internal bone loss is better offset in men. More women than men sustain fractures because their smaller skeleton incurs greater architectural damage and adapts less effectively by periosteal bone formation. The structural basis of bone fragility is determined before birth, takes root during growth, and gains full expression during ageing in both sexes.
Bone mass declines and the risk of fractures increases as people age, especially as women pass through the menopause. Hip fractures, the most serious outcome of osteoporosis, are becoming more frequent than before because the world's population is ageing and because the frequency of hip fractures is increasing by 1-3% per year in most areas of the world. Rates of hip fracture vary more widely from region to region than does the prevalence of vertebral fractures. Low bone density and previous fractures are risk factors for almost all types of fracture, but each type of fracture also has its own unique risk factors. Prevention of fractures with drugs could potentially be as expensive as medical treatment of fractures. Therefore, epidemiological research should be done and used to identify individuals at high-risk of disabling fractures, thereby allowing careful allocation of expensive treatments to individuals most in need.
The diagnosis of osteoporosis centres on the assessment of bone mineral density (BMD). Osteoporosis is defined as a BMD 2.5 SD or more below the average value for premenopausal women (T score < -2.5 SD). Severe osteoporosis denotes osteoporosis in the presence of one or more fragility fractures. The same absolute value for BMD used in women can be used in men. The recommended site for diagnosis is the proximal femur with dual energy X-ray absorptiometry (DXA). Other sites and validated techniques, however, can be used for fracture prediction. Although hip fracture prediction with BMD alone is at least as good as blood pressure readings to predict stroke, the predictive value of BMD can be enhanced by use of other factors, such as biochemical indices of bone resorption and clinical risk factors. Clinical risk factors that contribute to fracture risk independently of BMD include age, previous fragility fracture, premature menopause, a family history of hip fracture, and the use of oral corticosteroids. In the absence of validated population screening strategies, a case finding strategy is recommended based on the finding of risk factors. Treatment should be considered in individuals subsequently shown to have a high fracture risk. Because of the many techniques available for fracture risk assessment, the 10-year probability of fracture is the desirable measurement to determine intervention thresholds. Many treatments can be provided cost-effectively to men and women if hip fracture probability over 10 years ranges from 2% to 10% dependent on age.
The aim of treatment of postmenopausal osteoporosis is to reduce the frequency of vertebral and non-vertebral fractures (especially at the hip), which are responsible for morbidity associated with the disease. Results of large placebo controlled trials have shown that alendronate, raloxifene, risedronate, the 1-34 fragment of parathyroid hormone, and nasal calcitonin, greatly reduce the risk of vertebral fractures. Furthermore, a large reduction of non-vertebral fractures has been shown for alendronate, risedronate, and the 1-34 fragment of parathyroid hormone. Calcium and vitamin D supplementation is not sufficient to treat individuals with osteoporosis but is useful, especially in elderly women in care homes. Hormone replacement therapy remains a valuable option for the prevention of osteoporosis in early postmenopausal women. Choice of treatment depends on age, the presence or absence of prevalent fractures, especially at the spine, and the degree of bone mineral density measured at the spine and hip. Non-pharmacological interventions include adequate calcium intake and diet, selected exercise programmes, reduction of other risk factors for osteoporotic fractures, and reduction of the risk of falls in elderly individuals.
We have investigated the effects of GH treatment on bone turnover, bone size, bone mineral density (BMD), and bone mineral content (BMC) in 29 men, 27-62 yr old, with idiopathic osteoporosis. The patients were randomly assigned to treatment with GH, either as continuous treatment with daily injections of 0.4 mg GH/d (group A, n = 14) or as intermittent treatment with 0.8 mg GH/d for 14 d every 3 months (group B, n = 15). All patients were treated with GH for 24 months, with a follow-up period of 12 months, and also received 500 mg calcium and 400 U vitamin D3 daily during all 36 months. Fasting morning urine and serum samples were obtained for assay of IGF-I, bone markers, and routine laboratory tests at baseline, after 1, 12, 24, and 36 months. Body composition, BMD, and BMC were determined by dual-energy x-ray absorptiometry at baseline and every 6 months. After 2 yr, there was an increase in BMD in lumbar spine (by 4.1%) in group A, and in total body (by 2.6%) in group A and (by 2.7%) in group B. BMC of the total body and lean body mass increased, whereas fat mass decreased in both treatment groups. After 36 months, the BMD and BMC in lumbar spine and total body had increased further in both groups. We conclude that 2 yr of intermittent or continuous treatment with GH in men with idiopathic osteoporosis results in an increase in BMD and BMC that is sustained for at least 1 yr post treatment.
Type I collagen fragments are the most sensitive markers of bone resorption in osteoporosis. Currently, all available type I collagen-related bone resorption markers detect in serum and/or urine fragments arising from the telopeptide region of the molecule. Our aim was to evaluate the technical and clinical performances of a new assay detecting in urine a degradation fragment originating from the helical part of type I collagen and consisting of the 620-633 sequence of the alpha1 chain. Urinary helical peptide was measured with a new ELISA (Metra Helical peptide, Quidel Corporation). Results were compared with those of urinary C-terminal cross-linking type I collagen of type I collagen (CTX), an established bone resorption marker. We measured urinary helical peptide levels in 89 healthy women (age 31-89 years) and in 59 postmenopausal women involved in two randomized studies of the efficacy of alendronate (10 mg/day; n = 20) and transdermal 17beta estradiol (50 microg/day; n = 39). The within-run and between-run CVs were < or = 7.3 and 8.7%, respectively. In 59 healthy women, urinary helical peptide levels highly correlated with those of urinary CTX (r = 0.78, P < 0.0001). The long-term intraindividual variability assessed over 6 months in 18 untreated postmenopausal women was 24%. Compared to 24 premenopausal women, urinary helical peptide was 42% (P < 0.0001) higher in 65 postmenopausal women (mean age, 60 years), an increase comparable to that of urinary CTX (+ 47%, P < 0.0001). Urinary helical peptide levels decreased by 72% (P < 0.0001) after 3 months of alendronate treatment and by 59% (P < 0.0001) after 6 months of transdermal estrogen therapy. These changes were of similar magnitude to those of urinary CTX (-69 and -62%, respectively; NS compared with changes in helical peptide). In women treated with transdermal 17beta estradiol, the percentage of change of urinary helical peptide and urinary CTX at 6 months significantly correlated with the change in spinal bone mineral density after 2 years (r = -0.58, P = 0.002, and r = -0.52, P = 0.006, for urinary helical peptide and CTX, respectively). This new assay for type I collagen helical peptide has demonstrated adequate analytical performance and was highly correlated with urinary CTX, an established type I collagen C-telopeptide bone resorption marker. The test was a sensitive indicator of the antiresorptive effects of bisphosphonate and estrogens in postmenopausal women. This new bone resorption marker should be useful for the clinical investigation of patients with osteoporosis.
Androgen-deprivation therapy (ADT) is prescribed with increasing frequency for men with prostate carcinoma. There is growing concern about the effects of such therapy on the skeleton. In the current review, the authors addressed the current research, diagnostic methods, and treatment recommendations for bone loss and osteoporosis in men with prostate carcinoma who received ADT.
Data were obtained from electronic literature searches (for the years 1986 through 2002) and from abstracts and meeting proceedings. All randomized and nonrandomized clinical trials, retrospective studies, and cross-sectional studies of osteoporosis in men with prostate carcinoma who received ADT with or without other therapies were reviewed.
The findings confirmed that ADT resulted in significant bone loss in men with prostate carcinoma. Bone mineral density (BMD) of the hip, as measured by dual-energy X-ray absorptiometry (DXA), is considered the preferred site of assessment in older men. Spinal BMD is equally important, although careful interpretation of spinal DXA values is required, because of coexisting facet joint disease and extravertebral calcification. Osteoporosis is diagnosed when BMD is > 2.5 standard deviations below a reference mean. Men with prostate carcinoma who were treated with ADT had average BMD measurements below those of eugonadal men. Rates of bone loss ranged from 2% to 8% in the lumbar spine and from 1.8% to 6.5% in the femoral neck during the initial 12 months of continuous ADT. Retrospective data indicated an increased risk of fracture in men with prostate carcinoma who were treated with ADT.
For men with prostate carcinoma who are at high risk for osteoporosis and fractures, clinical management should be dictated by the results of radiographic and DXA skeletal assessment.
To review the literature describing the association of osteoporosis (OP) with scleroderma (SSc).
A Medline (PubMed) search identified all studies from 1966 to 2004 that investigated the association between OP and SSc. Search terms included "scleroderma," "systemic sclerosis," "osteoporosis, " "bone mineral density," "bone densitometry," and "prevalence."
Eight case control studies and 1 retrospective study (comparing OP status to a reference standard) were identified. There is no clear association between bone mineral density (BMD) scores and scleroderma. Two of 4 studies have reported lower BMD scores in SSc, but appear not to have considered possible confounding risk factors. Earlier age of menopause has been reported in 2 of 3 studies, and thus, may be a confounder in some samples of women with SSc. Studies of bone metabolism markers have not provided any consistent explanatory mechanism for increased OP in SSc, and such markers may be unreliable in SSc as these are affected by the altered collagen turnover and fibrosis characteristic of SSc.
It is unknown whether OP is truly increased in SSc or whether this association has been observed in some studies as a result of other confounding risk factors for OP. Clinical heterogeneity of SSc study samples and small sample sizes have contributed to the difficulty in obtaining valid estimates of the risk for the development of OP. There is no strong evidence in the literature for consistently lower BMD scores in SSc, or for altered biomarkers of bone resorption. Earlier menopause, corticosteroid use in some patients, and other factors secondary to SSc (such as malabsorption and inflammation), may be causal factors or may be confounders in studies of OP in SSc.
Scurvy occurs in individuals who eat inadequate amounts of fresh fruit or vegetables, often because of dietary imbalances related to advanced age or homelessness. Asthenia, vascular purpura, bleeding, and gum abnormalities are the main symptoms. In 80% of cases, the manifestations of scurvy include musculoskeletal symptoms consisting of arthralgia, myalgia, hemarthrosis, and muscular hematomas. Vitamin C depletion is responsible for structural collagen alterations, defective osteoid matrix formation, and increased bone resorption. Imaging studies may show osteolysis, joint space loss, osteonecrosis, osteopenia, and/or periosteal proliferation. Trabecular and cortical osteoporosis is common. Children experience severe lower limb pain related to subperiosteal bleeding. Laboratory tests show nonspecific abnormalities including anemia and low levels of cholesterol and albumin. The finding of a serum ascorbic acid level lower than 2.5 mg/l confirms the diagnosis. Vitamin C supplementation ensures prompt resolution of the symptoms.
On Dec, 31, 1664, Samuel Pepys, taking stock of the past year, confided to his diary: “I bless God, I never have been in so good plight as to my health … but I am at a great loss to know whether it be my Hare's foot, or taking every morning a pill of Turpentine, or my having left off the wearing of a gowne”.1 We would be wrong to think that our current preoccupation with health is new. People have always been intensely concerned with what makes them sick and what keeps them well. What has changed since the 17th century is our expectations, not only of effective treatment, but also of a satisfactory explanation as to why we have become ill. For Pepys, illness and disease had to be accepted as part of the human predicament. Their causes were a matter of conjecture, and avoiding them required magic and good fortune. Nowadays, luck and magic have been replaced by risk factors. Health promotion messages lead people to believe that by adopting the right lifestyle they will stay well. Naturally, if they become ill, they demand a reason. If such a reason is not forthcoming, they imagine that this is because medical knowledge is still incomplete, and that further research will soon reveal the answer. The view that better knowledge of causation will allow us to understand why some people develop a disease whereas others do not, is widely shared by doctors and medical scientists. Think how often the introduction to a grant application contains the phrase, “the causes of X are poorly understood”, by which the authors imply that there are important, but as yet unidentified, causes waiting to be discovered and that, provided the committee has the vision to award funding, better prediction of disease occurrence and more effective prevention could be possible. Though we smile at Pepys' hare's foot amulet and turpentine pill, his doubts about their effectiveness might contain more truth than the aspirations of the grant applicants. Obviously, a patient with a disease must have been exposed to a combination of causes sufficient to induce that disease, but it does not necessarily follow that these causes are measurable or even identifiable. An analogy can be drawn with the throw of a die. The fact that a six is rolled does not mean that the die was heavily exposed to any risk factors for that outcome. Instead, this result is due to the operation of a complex set of circumstances (dimensions, shape, and weight of the die; the exact position of its centre of gravity; forces acting on it and its height above the ground when thrown; viscosity of the air; contour and elastic properties of the surface on which it landed, and so on), none of which could be shown to have a consistent effect on its own on whether the die rolls six—except, of course, in the trivial circumstance of dropping it very gently from minimum height with the six face up. In this essay we review the nature of disease causation, and argue that the role of stochastic processes is underappreciated. Advances in understanding of pathogenic mechanisms or genetic susceptibility might not enable us to explain why one person gets a disease and another does not.
Systemic sclerosis. Dermatology in internal medicine
- S Shuster
Shuster S. Systemic sclerosis. Dermatology in internal medicine. Oxford: Oxford University Press; 1978. p. 204–208.