Archives of Osteoporosis 12/2013; 8(1-2):122.
ABSTRACT: Abstract Background Vitamin D insufficiency has deleterious consequences on health outcomes. In elderly or postmenopausal women, it may exacerbate osteoporosis. Scope There is currently no clear consensus on definitions of vitamin D insufficiency or minimal targets for vitamin D concentrations and proposed targets vary with the population. In view of the potential confusion for practitioners on when to treat and what to achieve, the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) convened a meeting to provide recommendations for clinical practice, to ensure the optimal management of elderly and postmenopausal women with regard to vitamin D supplementation. Findings Vitamin D has both skeletal and extra-skeletal benefits. Patients with serum 25-hydroxyvitamin D (25-(OH)D) levels <50 nmol/L have increased bone turnover, bone loss, and possibly mineralization defects compared with patients with levels >50 nmol/L. Similar relationships have been reported for frailty, nonvertebral and hip fracture, and all-cause mortality, with poorer outcomes at <50 nmol/L. Conclusion The ESCEO recommends that 50 nmol/L (i.e. 20 ng/mL) should be the minimal serum 25-(OH)D concentration at the population level and in patients with osteoporosis to ensure optimal bone health. Below this threshold, supplementation is recommended at 800 to 1000 IU/day. Vitamin D supplementation is safe up to 10 000 IU day (upper limit of safety) (resulting in an upper limit of adequacy of 125 nmol/L 25-(OH)D). Daily consumption of calcium- and vitamin D-fortified food products (e.g. yoghurt or milk) can help improve vitamin D intake. Above the threshold of 50 nmol/L, there is no clear evidence for additional benefits of supplementation. On the other hand, in fragile elderly subjects who are at elevated risk for falls and fracture, the ESCEO recommends a minimal serum 25-(OH)D level of 75 nmol/L (i.e. 30 ng/mL), for the greatest impact on fracture.
Current Medical Research and Opinion 01/2013; · 2.38 Impact Factor
ABSTRACT: The quality of life during the first 4 months after fracture was estimated in 2,808 fractured patients from 11 countries. Analysis showed that there were significant differences in the quality of life (QoL) loss between countries. Other factors such as QoL prior fracture and hospitalisation also had a significant impact on the QoL loss. INTRODUCTION: The International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS) was initiated in 2007 with the objective of estimating costs and quality of life related to fractures in several countries worldwide. The ICUROS is ongoing and enrols patients in 11 countries (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain, UK and the USA). The objective of this paper is to outline the study design of ICUROS and present results regarding the QoL (measured using the EQ-5D) during the first 4 months after fracture based on the patients that have been thus far enrolled ICUROS. METHODS: ICUROS uses a prospective study design where data (costs and quality of life) are collected in four phases over 18 months after fracture. All countries use the same core case report forms. Quality of life was collected using the EQ-5D instrument and a time trade-off questionnaire. RESULTS: The total sample for the analysis was 2,808 patients (1,273 hip, 987 distal forearm and 548 vertebral fracture). For all fracture types and countries, the QoL was reduced significantly after fracture compared to pre-fracture QoL. A regression analysis showed that there were significant differences in the QoL loss between countries. Also, a higher level of QoL prior to the fracture significantly increased the QoL loss and patients who were hospitalised for their fracture also had a significantly higher loss compared to those who were not. CONCLUSIONS: The findings in this study indicate that there appear to be important variations in the QoL decrements related to fracture between countries.
Osteoporosis International 01/2013; · 4.58 Impact Factor
ABSTRACT: The objective was to undertake a health economic analysis of denosumab for the treatment of osteoporosis in women from the UK, using the FRAX® tool. Denosumab was cost-effective in women with a risk of major osteoporotic fracture meeting or exceeding approximately 20 % who are unable to take, comply with or tolerate generic alendronate. INTRODUCTION: Denosumab is a novel biologic agent developed for the treatment of osteoporosis, which has been shown to reduce the risk of fractures in a phase-III trial. The objective of the present study was to undertake a health economic analysis of denosumab in women from the UK. Ten-year probabilities of a major osteoporotic fracture at which denosumab is a cost-effective alternative to no treatment, generic alendronate, risedronate and strontium ranelate were estimated. METHODS: A previously published Markov model was adapted to incorporate fracture and mortality risk assessments based on absolute fracture probability, as estimated by FRAX®. The model included treatment persistence and residual effect after discontinuation. RESULTS: At a willingness-to-pay (WTP) of £30,000 per quality-adjusted life year and a 10-year fracture probability equivalent to a woman with a prior fragility fracture, denosumab was cost-effective compared to no treatment from the age of 70 years. At the same WTP, denosumab was-irrespective of age-cost-effective compared to no treatment at a major osteoporotic fracture probability of approximately 20 %. Denosumab was estimated to cost-effectively replace strontium, risedronate and generic alendronate at 10-year probabilities exceeding 11, 19 and 32 %, respectively. CONCLUSION: FRAX® facilitates the estimation of cost-effectiveness-based intervention thresholds applicable to patients with different combinations of clinical risk factors, which more closely matches the situation in clinical practice. Denosumab is cost-effective in patients with major osteoporotic fracture probabilities meeting or exceeding approximately 20 % who are unable to take, comply with or tolerate generic alendronate.
Osteoporosis International 12/2012; · 4.58 Impact Factor
ABSTRACT: This paper visualizes the available data on vitamin D status on a global map, examines the existing heterogeneities in vitamin D status and identifies research gaps.
A graphical illustration of global vitamin D status was developed based on a systematic review of the worldwide literature published between 1990 and 2011. Studies were eligible if they included samples of randomly selected males and females from the general population and assessed circulating 25-hydroxyvitamin D [25(OH)D] levels. Two different age categories were selected: children and adolescents (1-18 years) and adults (>18 years). Studies were chosen to represent a country based on a hierarchical set of criteria.
In total, 200 studies from 46 countries met the inclusion criteria, most coming from Europe. Forty-two of these studies (21 %) were classified as representative. In children, gaps in data were identified in large parts of Africa, Central and South America, Europe, and most of the Asia/Pacific region. In adults, there was lack of information in Central America, much of South America and Africa. Large regions were identified for which the mean 25(OH)D levels were below 50 nmol/L.
This study provides an overview of 25(OH)D levels around the globe. It reveals large gaps in information in children and adolescents and smaller but important gaps in adults. In view of the importance of vitamin D to musculoskeletal growth, development, and preservation, and of its potential importance in other tissues, we strongly encourage new research to clearly define 25(OH)D status around the world.
Archives of Osteoporosis 12/2012; 7(1-2):155-72.
ABSTRACT: The use of glucocorticoids in the treatment of medical disorders can lead to rapid bone loss and increased risk of fragility fracture. Updated clinical guidelines are needed that accommodate recent advances in fracture risk assessment and new pharmacological interventions to reduce fracture risk. This document serves as an appendix to the 2012 IOF-ECTS guidelines for the management of glucocorticoid-induced osteoporosis.
Archives of Osteoporosis 12/2012; 7(1-2):25-30.
ABSTRACT: This article describes the adaptation of a model assessing the incidence of osteoporotic fractures and prevalence of postmenopausal osteoporosis (PMO) in Germany. PURPOSE: The purpose of this paper is to estimate the epidemiological burden of PMO in Germany from 2010 to 2020. METHODS: For each year of the study, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using 1-year cycles until 2020. Health states were based on the number of fractures (1, 2 or ≥3) and deaths. Although the fracture site was not explicitly accounted for in the model structure, the site (hip, vertebral, non-hip non-vertebral) was tracked for each health state. Transition probabilities reflected the site-specific risk of death and of subsequent fractures. Model inputs included population size and life tables from 1970 to 2020, incidence of fracture and BMD by age in the general population (mean and standard deviation). RESULTS: In 2010, the number of osteoporotic fractures was estimated at 349,560 in women aged 50 years or more, including 80,177 hip and 48,550 vertebral fractures. By 2020, the population is expected to grow by 13.1 %. As a result, the number of fractures is predicted to increase by 15.2 %. The improvement in life expectancy is predicted to lead to a relatively smaller increase in the number of deaths attributable to fractures (+12.8 %), but also to an increase in the prevalence of women with multiple prior fractures (+25.5 %). CONCLUSION: The PMO disease model, first developed for Sweden, was adapted to Germany. Due to the ageing of the population, the number of osteoporotic fractures is expected to increase markedly by +15.2 % by 2020.
Archives of Osteoporosis 11/2012;
ABSTRACT: Aspects of osteoporosis in men, such as screening and identification strategies, definitions of diagnosis and intervention thresholds, and treatment options (both approved and in the pipeline) are discussed. INTRODUCTION: Awareness of osteoporosis in men is improving, although it remains under-diagnosed and under-treated. A European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) workshop was convened to discuss osteoporosis in men and to provide a report by a panel of experts (the authors). METHODS: A debate with an expert panel on preselected topics was conducted. RESULTS AND CONCLUSIONS: Although additional fracture data are needed to endorse the clinical care of osteoporosis in men, consensus views were reached on diagnostic criteria and intervention thresholds. Empirical data in men display similarities with data acquired in women, despite pathophysiological differences, which may not be clinically relevant. Men should receive treatment at a similar 10-year fracture probability as in women. The design of mixed studies may reduce the lag between comparable treatments for osteoporosis in women becoming available in men.
Bone 11/2012; · 4.02 Impact Factor
ABSTRACT: This article estimates the present and future burden of postmenopausal osteoporosis in France in women aged 50 years and over. METHODS: We adapted an existing model developed for Sweden to France. For each year of the study from 1970 to 2020, the 'incident cohort' (women experiencing a first osteoporotic fracture) was identified and run through a Markov model using annual cycles. Health states were based on the number of fractures (hip, vertebral, non-hip non-vertebral) and deaths. Transition probabilities reflected fracture site-specific risks of subsequent fractures and of death. Country-specific model inputs included population size and life tables from 1970 to 2020 and incidence of hip fracture. RESULTS: The model estimated that the number of postmenopausal osteoporotic women was expected to increase from 3.0 million to 3.4 million between 2010 and 2020 (+15.3 %). Assuming that the incidence of fracture by age group does not change over time, the model predicted that the overall number of osteoporotic fractures would increase from 204,234 fractures in 2010 to 241,261 in 2020 (+18.1 %), hip (20.3 %), vertebral (19.0 %) and non-hip non-vertebral fractures (17.0 %). CONCLUSION: The aging of the population is expected to drive a marked increase in the prevalence of osteoporosis and in the number of osteoporotic fractures. These data may assist future planning for appropriate heath care provision.
Archives of Osteoporosis 09/2012;
ABSTRACT: This review summarizes the available evidence-based data that form the basis for therapeutic intervention and covers the current status of glucocorticoid-induced osteoporosis (GIOP) management, regulatory requirements, and risk-assessment options. Glucocorticoids are known to cause bone loss and fractures, yet many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated. An European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis workshop was convened to discuss GIOP management and to provide a report by a panel of experts. An expert panel reviewed the available studies that discussed approved therapeutic agents, focusing on randomized and controlled clinical trials reporting on bone mineral density and/or fracture risk of at least 48 weeks' duration. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. The FRAX algorithm can be adjusted according to glucocorticoid dose. Available antiosteoporotic therapies such as bisphosphonates and teriparatide are efficacious in GIOP management. Several other agents approved for the treatment of postmenopausal osteoporosis may become available for GIOP. It is advised to stop antiosteoporotic treatment after glucocorticoid cessation, unless the patient remains at increased risk of fracture. Calcium and vitamin D supplementation as an osteoporosis-prevention measure is less effective than specific antiosteoporotic treatment. Fracture end-point studies and additional studies investigating specific subpopulations (pediatric, premenopausal, or elderly patients) would strengthen the evidence base and facilitate the development of intervention thresholds and treatment guidelines.
Calcified Tissue International 08/2012; 91(4):225-43. · 2.38 Impact Factor
ABSTRACT: Guidelines concerning the definition of failure of therapies used to reduce the risk of fracture are provided. INTRODUCTION: This study aims to provide guidelines concerning the definition of failure of therapies used to reduce the risk of fracture. METHODS: A working group of the Committee of Scientific Advisors of the International Osteoporosis Foundation was convened to define outcome variables that may assist clinicians in decision making. RESULTS: In the face of limited evidence, failure of treatment may be inferred when two or more incident fractures have occurred during treatment, when serial measurements of bone remodelling markers are not suppressed by anti-resorptive therapy and where bone mineral density continues to decrease. CONCLUSION: The provision of pragmatic criteria to define failure to respond to treatment provides an unmet clinical need and may stimulate research into an important issue.
Osteoporosis International 07/2012; · 4.58 Impact Factor
Osteoporosis International 06/2012; 23(9):2401-2. · 4.58 Impact Factor
ABSTRACT: Use of antidepressant medications that act on the serotonin system has been linked to detrimental impacts on bone mineral density (BMD), and to osteoporosis. This article reviews current evidence for such effects, and identifies themes for future research. Serotonin receptors are found in all major types of bone cell (osteoblasts, osteocytes, and osteoclasts), indicating an important role of the neuroendocrine system in bone. Observational studies indicate a complex relationship between depression, antidepressants, and fracture. First, the presence of depression itself increases fracture risk, in relation with decreased BMD and an increase in falls. A range of aspects of depression may operate, including behavioral factors (e.g., smoking and nutrition), biological changes, and confounders (e.g., comorbidities and concomitant medications). A substantial proportion of depressed patients receive antidepressants, mostly selective serotonin reuptake inhibitors (SSRIs). Some of these have been linked to decreased BMD (SSRIs) and increased fracture risk (SSRIs and tricyclic agents). Current use of SSRIs and tricyclics increases fracture risk by as much as twofold versus nonusers, even after adjustment for potential confounders. While there is a dose-response relationship for SSRIs, the effect does not appear to be homogeneous across the whole class of drugs and may be linked to affinity for the serotonin transporter system. The increase in risk is the greatest in the early stages of treatment, with a dramatic increase after initiation, reaching a peak within 1 month for tricyclics and 8 months for SSRIs. Treatment-associated increased risk diminishes towards baseline in the year following discontinuation. The body of evidence suggests that SSRIs should be considered in the list of medications that are risk factors for osteoporotic fractures.
Bone 05/2012; 51(3):606-13. · 4.02 Impact Factor
ABSTRACT: In order to update data underlying the Italian version of FRAX, we computed the national hip fracture incidence in Italy from hospitalization records for the year 2008. Mortality data and 10-year probabilities of major osteoporotic fractures were also updated. This revision will improve FRAX accuracy and reliability. INTRODUCTION: The original Italian version of FRAX® was based on five regional estimates of hip fracture risk undertaken up to 20 years previously. Our objective was to update hip fracture rates for the model with more recently derived data from the whole Italian population and more recent data on mortality. METHODS: We analyzed the Italian national hospitalization database for the year 2008 in order to compute age- and sex-specific hip fracture incidence rates. Re-hospitalisations of the same patients within 1 year were excluded from the analysis. Hip fracture incidence rates were computed for the age range of 40-100 years, whereas the original FRAX model lacked data on the youngest and oldest age groups. In addition, we used the national mortality data for the same year 2008 to update the model. Ten-year fracture probabilities were re-calculated on the basis of the new fracture incidence rates. RESULTS: The new hip fracture age- and sex-specific incidence rates were close to those used in the original FRAX tool, although some significant differences (not exceeding 25-30 %) were found for men aged 65-75 years and women under 55 years of age. In general, the revision resulted in decreased estimated 10-year probabilities in the younger age groups, whilst those in the older age groups were slightly increased. CONCLUSIONS: The Italian version of FRAX has been updated using the new fracture incidence rates. The impact of these revisions on FRAX is likely to increase the accuracy and reliability of FRAX in estimating 10-year fracture probabilities.
Osteoporosis International 05/2012; · 4.58 Impact Factor
ABSTRACT: SummaryUse of lumbar spine T-score or minimum T-score as a bone mineral density (BMD) input to the FRAX® algorithm led to miscalibration
compared with the recommended femoral neck input. Use of a weighted mean between the lumbar spine and femoral neck T-scores
was found to provide an arithmetically equivalent result to a previously described offset adjustment.
IntroductionFRAX assumes that the BMD input, when used in the calculation, is from the femoral neck. Use of other BMD inputs is not recommended,
but there are no studies describing how this affects the performance of FRAX.
MethodsTen-year probabilities of a major osteoporotic fracture were calculated with different BMD inputs for 20,477 women and men
aged 50years and older from Manitoba, Canada. FRAX probability calculated with femoral neck BMD was designated the reference
method. We also derived FRAX probabilities where the BMD input was based upon the lumbar spine T-score, minimum T-score (lumbar
spine or femoral neck), weighted mean T-score (lumbar spine or femoral neck), or used an adjustment for the spine–hip T-score
difference (offset). Fracture outcomes were assessed using a population-based administrative data repository.
ResultsAll FRAX models showed good risk stratification with minimal differences. There was no consistent improvement in FRAX performance
when lumbar spine or minimum T-score were used as inputs, but calibration was adversely affected due to higher mean fracture
probabilities compared with the femoral neck. The weighted mean T-score was found to be equivalent to the spine–hip T-score
offset adjustment, and both slightly improved risk classification without a change in calibration.
ConclusionsThe choice of BMD input to the FRAX model has a large effect on performance. The lumbar spine T-score or minimum T-score should
not be used as inputs to the FRAX algorithm. Use of a weighted mean between the lumbar spine and femoral neck T-scores slightly
improves risk classification.
KeywordsBone mineral density–Clinical risk factors–Fracture prediction–FRAX®–Osteoporosis
Osteoporosis International 04/2012; 23(3):853-860. · 4.58 Impact Factor
ABSTRACT: SummaryFracture probability assessed without bone mineral density (BMD) could potentially be sufficient for clinical decision making
in many individuals categorized as low or high fracture risk. For individuals falling in a moderate risk range, there is incremental
value in using BMD in the probability calculation as this appropriately reclassifies risk in over one third of the individuals.
IntroductionA new fracture risk assessment tool from the World Health Organization (FRAX®) estimates 10-year major osteoporotic and hip
fracture probabilities from multiple clinical risk factors with or without hip BMD. The objective of this study is to determine
whether fracture probability derived without BMD can be used to identify individuals who would be designated for treatment.
MethodsA historical cohort of 36,730 women and 2,873 men aged 50years and older drawn from the Manitoba Bone Density Program database,
which contains clinical BMD results for the Province of Manitoba, Canada, was included in the study.
ResultsWhen 10-year probability for major osteoporotic fracture estimated without knowledge of BMD was high (≥20%), the vast majority
(92.8%) qualified for intervention under the National Osteoporosis Foundation (NOF) guidelines, whereas among those at low
risk (<10%), the vast majority (80.5%) did not satisfy any NOF intervention criteria. The benefit of including BMD in the
risk assessment was greatest among those initially at moderate risk (10–19%) when fracture probability was derived without
BMD, but this represented only 29.4% of the cohort (9.3% of those aged <65years and 48.7% of those ≥65years).
ConclusionsFracture probability derived without BMD is able to risk stratify women in terms of future fracture risk and could potentially
be sufficient for clinical decision making in many of those designated at low or high fracture risk.
KeywordsAdministrative data–Bone mineral density–Dual-energy X-ray absorptiometry–Fracture prediction–FRAX–Osteoporosis
Osteoporosis International 04/2012; 23(1):75-85. · 4.58 Impact Factor
ABSTRACT: IntroductionIt has been suggested that bone mineral density (BMD) measurements should be made at multiple sites, and that the lowest T–score
should be taken for the purpose of diagnosing osteoporosis.
PurposeThe aim of this study was to examine the use of BMD measurements at the femoral neck and lumbar spine alone and in combination
for fracture prediction.
MethodsWe studied 19,071 individuals (68% women) from six prospective population-based cohorts in whom BMD was measured at both sites
and fracture outcomes documented over 73,499 patient years. BMD values were converted to Z-scores, and the gradient of risk
for any osteoporotic fracture and for hip fracture was examined by using a Poisson model in each cohort and each gender separately.
Results of the different studies were merged using weighted β-coefficients.
ResultsThe gradients of risk for osteoporotic fracture and for hip fracture were similar in men and women. In men and women combined,
the risk of any osteoporotic fracture increased by 1.51 [95% confidence interval (CI)=1.42–1.61] per standard deviation (SD)
decrease in femoral-neck BMD. For measurements made at the lumbar spine, the gradient of risk was 1.47 (95% CI=1.38–1.56).
Where the minimum of the two values was used, the gradient of risk was similar (1.55; 95% CI=1.45–1.64). Higher gradients
of risk were observed for hip fracture outcomes: with BMD at the femoral neck, the gradient of risk was 2.45 (95% CI=2.10–2.87),
with lumbar BMD was 1.57 (95% CI=1.36–1.82), and with the minimum value of either femoral neck and lumbar spine was 2.11 (95%
CI=1.81–2.45). Thus, selecting the lowest value for BMD at either the femoral neck or lumbar spine did not increase the predictive
ability of BMD tests. By contrast, the sensitivity increased so that more individuals were identified but at the expense of
specificity. Thus, the same effect could be achieved by using a less stringent T–score for the diagnosis of osteoporosis.
ConclusionsSince taking the minimum value of the two measurements does not improve predictive ability, its clinical utility for the diagnosis
of osteoporosis is low.
Osteoporosis International 04/2012; 17(4):527-534. · 4.58 Impact Factor
ABSTRACT: SummaryMost patients designated as high risk of fracture using fracture risk assessment tool (FRAX®) with femoral neck bone mineral density (BMD) (i.e., 10-year major osteoporotic fracture probability exceeding 20% or hip
fracture exceeding 3%) have one or more T-scores in the osteoporotic range; conversely, almost no high risk patients have
normal T-scores at all bone mineral density measurement sites.
IntroductionWe determined the agreement between a FRAX® designation of high risk of fracture [defined as 10-year major osteoporotic fracture probability (≥20%) or hip fracture probability
(≥3%)] and the WHO categorizations of bone mineral density according to T-score.
MethodsTen-year FRAX® probabilities calculated with femoral neck BMD were derived using both Canadian and US white tools for a large clinical cohort
of 36,730 women and 2,873 men age 50years and older from Manitoba, Canada. Individuals were classified according to FRAX
fracture probability and BMD T-scores alone.
ResultsMost individuals designated by FRAX as high risk of major osteoporotic fracture had a T-score in the osteoporotic range at
one or more BMD measurement sites (85% with Canadian tool and 83% with US white tool). The majority of individuals deemed
at high risk of hip fracture had one or more T-scores in the osteoporotic range (66% with Canadian tool and 64% with US white
tool). Conversely, there were extremely few individuals (<1%) who were at high risk of major osteoporotic or hip fracture
with normal T-scores at all BMD measurement sites.
ConclusionsA FRAX designation of high risk of fracture is usually associated with a densitometric diagnosis of osteoporosis.
KeywordsBone mineral density–Clinical risk factors–Fracture prediction–FRAX®
Osteoporosis International 04/2012; 23(1):391-397. · 4.58 Impact Factor
ABSTRACT: IntroductionIntervention thresholds (ITs), the 10-year hip fracture risk at which treatment can be considered to be cost-effective, have previously been estimated for Sweden and the UK.ObjectiveThe aim of this study was to provide a Markov cohort model platform for a multinational estimation of thresholds at which intervention becomes cost-effective and to investigate and determine the main factors behind differences in these thresholds between countries.Results and discussionIntervention thresholds were estimated for Australia, Germany, Japan, Sweden, Spain, the UK and USA using a societal perspective. The model was populated with as much relevant country-specific data as possible. Intervention was assumed to be given for 5years and to decrease the risk of all osteoporotic fractures by 35%. The societal willingness to pay (WTP) for a quality-adjusted life-year (QALY) gained was set to the gross domestic product (GDP) per capita multiplied by two. In the base case analysis, the 10-year hip fracture probability at which intervention became cost-effective varied across ages and countries. For women starting therapy at an age of 70years, the IT varied from a hip fracture probability of 5.6% in Japan to 14.7% in Spain. The main factors explaining differences in the IT between countries were the WTP for a QALY gained, fracture-related costs and intervention costs.ConclusionThe ITs presented in this paper are appropriate for use in treatment guidelines that consider health economic aspects, and they can be used in combination with fracture risk prediction algorithms to improve the selection of patients who are suitable for osteoporotic intervention.
Osteoporosis International 04/2012; 17(10):1459-1471. · 4.58 Impact Factor
ABSTRACT: SummaryThe International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry and Laboratory Medicine
(IFCC) recommend that a marker of bone formation (serum procollagen type I N propeptide, s-PINP) and a marker of bone resorption
(serum C-terminal telopeptide of type I collagen, s-CTX) are used as reference analytes for bone turnover markers in clinical
IntroductionBone turnover markers (BTM) predict fracture risk, and treatment-induced changes in specific markers account for a substantial
proportion of fracture risk reduction. The aims of this report were to determine their clinical potential in the prediction
of fracture risk and for monitoring the treatment of osteoporosis and to set an appropriate research agenda.
MethodsEvidence from prospective studies was gathered through literature review of the PUBMED database between the years 2000 and
2010 and the systematic review of the Agency for Healthcare Research and Quality up to 2001.
ResultsHigh levels of BTMs may predict fracture risk independently from bone mineral density in postmenopausal women. They have been
used for this purpose in clinical practice for many years, but there is still a need for stronger evidence on which to base
practice. BTMs provide pharmacodynamic information on the response to osteoporosis treatment, and as a result, they are widely
used for monitoring treatment in the individual. However, their clinical value for monitoring is limited by inadequate appreciation
of the sources of variability, by limited data for comparison of treatments using the same BTM and by inadequate quality control.
IOF/IFCC recommend one bone formation marker (s-PINP) and one bone resorption marker (s-CTX) to be used as reference markers
and measured by standardised assays in observational and intervention studies in order to compare the performance of alternatives
and to enlarge the international experience of the application of markers to clinical medicine.
ConclusionBTM hold promise in fracture risk prediction and for monitoring treatment. Uncertainties over their clinical use can be in
part resolved by adopting international reference standards.
KeywordsBone makers–Bone turnover–Fracture risk–IOF–Monitoring treatment–Reference standards
Osteoporosis International 04/2012; 22(2):391-420. · 4.58 Impact Factor