Previous fracture and subsequent fracture risk: a meta-analysis to update FRAX.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. INTRODUCTION: The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). METHODS: We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted ß-coefficients. RESULTS: A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72-2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69-2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63-2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62-2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. CONCLUSION: A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Update of the fracture risk prediction tool FRAX: a systematic review of potential cohorts and analysis plan.

We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. INTRODUCTION: The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors. METHODS: A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible. RESULTS: Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed. CONCLUSIONS: These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).

Reference microarchitectural values measured by HR-pQCT in a Franco-Swiss cohort of young adult women.

Bone microarchitecture assessed by high-resolution peripheral quantitative computed tomography varies across populations of different origin. The study presents a reference dataset of microarchitectural parameters in a homogeneous group of participants aged within 22-27 range determined by a discriminant analysis of a larger cross-sectional cohort of 339 women. INTRODUCTION: High-resolution peripheral quantitative computed tomography (HR-pQCT) non-invasively measures three-dimensional bone microarchitectural parameters and volumetric bone mineral density. Previous studies established normative reference HR-pQCT datasets for several populations, but there were few data assessed in a reference group of young women with Caucasian ethnicity living in Western Europe. It is important to obtain different specific reference dataset for a valid interpretation of cortical and trabecular microarchitecture data. The aim of our study was to find the population with the most optimal bone status in order to establish a descriptive reference HR-pQCT dataset in a young and healthy normal-weight female cohort living in a European area including Geneva, Switzerland, Lyon and Saint-Etienne, France. METHODS: We constituted a cross-sectional cohort of 339 women aged 19-41 years with a BMI > 18 and < 30 kg/m2. All participants had HR-pQCT measurements at both non-dominant distal radius and tibia sites. RESULTS: We observed that microarchitectural parameters begin to decline before the age of 30 years. Based on a discriminant analysis, the optimal bone profile in this population was observed between the age range of 22 to 27 years. Consequently, we considered 43 participants aged 22-27 years to establish a reference dataset with median values and percentiles. CONCLUSION: This is the first study providing reference values of HR-pQCT measurements considering specific age bounds in a Franco-Swiss female cohort at the distal radius and tibia sites.

Perspectives on the non-invasive evaluation of femoral strength in the assessment of hip fracture risk.

We reviewed the experimental and clinical evidence that hip bone strength estimated by BMD and/or finite element analysis (FEA) reflects the actual strength of the proximal femur and is associated with hip fracture risk and its changes upon treatment. INTRODUCTION: The risk of hip fractures increases exponentially with age due to a progressive loss of bone mass, deterioration of bone structure, and increased incidence of falls. Areal bone mineral density (aBMD), measured by dual-energy X-ray absorptiometry (DXA), is the most used surrogate marker of bone strength. However, age-related declines in bone strength exceed those of aBMD, and the majority of fractures occur in those who are not identified as osteoporotic by BMD testing. With hip fracture incidence increasing worldwide, the development of accurate methods to estimate bone strength in vivo would be very useful to predict the risk of hip fracture and to monitor the effects of osteoporosis therapies. METHODS: We reviewed experimental and clinical evidence regarding the association between aBMD and/orCT-finite element analysis (FEA) estimated femoral strength and hip fracture risk as well as their changes with treatment. RESULTS: Femoral aBMD and bone strength estimates by CT-FEA explain a large proportion of femoral strength ex vivo and predict hip fracture risk in vivo. Changes in femoral aBMD are strongly associated with anti-fracture efficacy of osteoporosis treatments, though comparable data for FEA are currently not available. CONCLUSIONS: Hip aBMD and estimated femoral strength are good predictors of fracture risk and could potentially be used as surrogate endpoints for fracture in clinical trials. Further improvements of FEA may be achieved by incorporating trabecular orientations, enhanced cortical modeling, effects of aging on bone tissue ductility, and multiple sideway fall loading conditions.

Determinants, consequences and potential solutions to poor adherence to anti-osteoporosis treatment: results of an expert group meeting organized by the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Osteoporosis Foundation (IOF).

Many patients at increased risk of fractures do not take their medication appropriately, resulting in a substantial decrease in the benefits of drug therapy. Improving medication adherence is urgently needed but remains laborious, given the numerous and multidimensional reasons for non-adherence, suggesting the need for measurement-guided, multifactorial and individualized solutions. INTRODUCTION: Poor adherence to medications is a major challenge in the treatment of osteoporosis. This paper aimed to provide an overview of the consequences, determinants and potential solutions to poor adherence and persistence to osteoporosis medication. METHODS: A working group was organized by the European Society on Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal diseases (ESCEO) to review consequences, determinants and potential solutions to adherence and to make recommendations for practice and further research. A systematic literature review and a face-to-face experts meeting were undertaken. RESULTS: Medication non-adherence is associated with increased risk of fractures, leading to a substantial decrease in the clinical and economic benefits of drug therapy. Reasons for non-adherence are numerous and multidimensional for each patient, depending on the interplay of multiple factors, suggesting the need for multifactorial and individualized solutions. Few interventions have been shown to improve adherence or persistence to osteoporosis treatment. Promising actions include patient education with counselling, adherence monitoring with feedback and dose simplification including flexible dosing regimen. Recommendations for practice and further research were also provided. To adequately manage adherence, it is important to (1) understand the problem (initiation, implementation and/or persistence), (2) to measure adherence and (3) to identify the reason of non-adherence and fix it. CONCLUSION: These recommendations are intended for clinicians to manage adherence of their patients and to researchers and policy makers to design, facilitate and appropriately use adherence interventions.

Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis.

Life expectancy of people living with HIV (PLWH) is reaching similar length as in the general population. Accordingly, age-related comorbidities, including osteoporosis, are increasing. Fracture risk is higher and increases approximately 10 years earlier in PLWH. Classical risk factors of bone fragility are highly prevalent in PLWH but factors specific for HIV infection itself and the type of antiretroviral therapy (ART) (triple combination antiretroviral therapy) regimen (especially tenofovir and protease inhibitors) also contribute to bone loss. The majority of bone loss occurs during virus activity and at initiation of ART (immune reconstitution) and is associated with an increase of bone resorption (upregulation RANKL). Recent data indicate that calcium and vitamin D supplements as ART initiation lower BMD loss. The reduction of tenofovir plasma concentrations with tenofovir alafenamide attenuates BMD loss but it remains unknown whether it will contribute to reduce fracture risk. Hence, special considerations for the management of bone fragility in PLWH are warranted. Based on the current state of epidemiology and pathophysiology of osteoporosis in PLWH, we provide the consensus of the Swiss Association against Osteoporosis on best practice for diagnosis, prevention, and management of osteoporosis in this population. Periodic assessment of fracture risk is indicated in all HIV patients and general preventive measures should be implemented. All postmenopausal women, men above 50 years of age, and patients with other clinical risk for fragility fractures qualify for BMD measurement. An algorithm clarifies when treatment with bisphosphonates and review of ART regimen in favour of more bone-friendly options are indicated.

Associations between radius low-frequency axial ultrasound velocity and bone fragility in elderly men and women.

An exploratory study in elderly women and men from the Geneva Retirees Cohort indicates that low-frequency quantitative ultrasound measurement at the radius captures aBMD, bone size, and cortical tissue mineral density and might be used for screening purposes prior to DXA to evaluate fracture risk. INTRODUCTION: The contribution of distal radius bone mineral density (BMD) and cortical microstructure to fracture risk has recently been demonstrated. In this exploratory study, we investigated whether low-frequency quantitative ultrasound measurement at the distal radius may capture the peripheral determinants of bone fragility assessed with dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT). METHODS: Low-frequency velocity (VLF) was measured at the radius using OsCare Sono®, a portable axial transmission ultrasonometer, in 271 community-dwelling postmenopausal women and men (age 71.5 ± 1.4 years) from the Geneva Retirees Cohort. Cortical (Ct) and trabecular (Tb) volumetric (v) BMD and microstructure at the distal radius were assessed by HR-pQCT, in addition to areal (a) BMD by DXA, at the same time point. RESULTS: VLF was highly correlated with aBMD at the distal third radius (r = 0.72, p < 0.001). For microstructure parameters, the highest correlation was observed with cortical area (r = 0.59, p < 0.001). VLF also captured bone geometry (total area) and cortical tissue mineral density independently of aBMD. In models adjusted for age and sex, VLF was significantly associated with prevalent low-trauma fractures [OR 95%CI for one SD decrease of VLF 1.50 (1.05, 2.14), p = 0.024], with discrimination performance comparable to femoral neck or distal radius aBMD. CONCLUSION: Measurement of VLF at the radius captures aBMD, bone size, and cortical tissue mineral density and might be used for screening purposes prior to DXA to evaluate fracture risk.

Fermented dairy products consumption is associated with attenuated cortical bone loss independently of total calcium, protein, and energy intakes in healthy postmenopausal women.

A longitudinal analysis of bone microstructure in postmenopausal women of the Geneva Retirees Cohort indicates that age-related cortical bone loss is attenuated at non-bearing bone sites in fermented dairy products consumers, not in milk or ripened cheese consumers, independently of total energy, calcium, or protein intakes. INTRODUCTION: Fermented dairy products (FDP), including yogurts, provide calcium, phosphorus, and proteins together with prebiotics and probiotics, all being potentially beneficial for bone. In this prospective cohort study, we investigated whether FDP, milk, or ripened cheese consumptions influence age-related changes of bone mineral density (BMD) and microstructure. METHODS: Dietary intakes were assessed at baseline and after 3.0 ± 0.5 years with a food frequency questionnaire in 482 postmenopausal women enrolled in the Geneva Retirees Cohort. Cortical (Ct) and trabecular (Tb) volumetric (v) BMD and microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computerized tomography, in addition to areal (a) BMD and body composition by dual-energy X-ray absorptiometry, at the same time points. RESULTS: At baseline, FDP consumers had lower abdominal fat mass and larger bone size at the radius and tibia. Parathyroid hormone and ß-carboxyterminal cross-linked telopeptide of type I collagen levels were inversely correlated with FDP consumption. In the longitudinal analysis, FDP consumption (mean of the two assessments) was associated with attenuated loss of radius total vBMD and of Ct vBMD, area, and thickness. There was no difference in aBMD and at the tibia. These associations were independent of total energy, calcium, or protein intakes. For other dairy products categories, only milk consumption was associated with lower decrease of aBMD and of failure load at the radius. CONCLUSION: In this prospective cohort of healthy postmenopausal women, age-related Ct bone loss was attenuated at non-bearing bone sites in FDP consumers, not in milk or ripened cheese consumers, independently of total energy, calcium, or protein intakes. STUDY REGISTRATION: ISRCTN11865958 ( http://www.isrctn.com ).

Benefits and safety of dietary protein for bone health-an expert consensus paper endorsed by the European Society for Clinical and Economical Aspects of Osteopororosis, Osteoarthritis, and Musculoskeletal Diseases and by the International Osteoporosis Foundation.

A summary of systematic reviews and meta-analyses addressing the benefits and risks of dietary protein intakes for bone health in adults suggests that dietary protein levels even above the current RDA may be beneficial in reducing bone loss and hip fracture risk, provided calcium intakes are adequate. Several systematic reviews and meta-analyses have addressed the benefits and risks of dietary protein intakes for bone health in adults. This narrative review of the literature summarizes and synthesizes recent systematic reviews and meta-analyses and highlights key messages. Adequate supplies of dietary protein are required for optimal bone growth and maintenance of healthy bone. Variation in protein intakes within the "normal" range accounts for 2-4% of BMD variance in adults. In older people with osteoporosis, higher protein intake (≥ 0.8-g/kg body weight/day, i.e., above the current RDA) is associated with higher BMD, a slower rate of bone loss, and reduced risk of hip fracture, provided that dietary calcium intakes are adequate. Intervention with dietary protein supplements attenuate age-related BMD decrease and reduce bone turnover marker levels, together with an increase in IGF-I and a decrease in PTH. There is no evidence that diet-derived acid load is deleterious for bone health. Thus, insufficient dietary protein intakes may be a more severe problem than protein excess in the elderly. Long-term, well-controlled randomized trials are required to further assess the influence of dietary protein intakes on fracture risk.

Interaction between LRP5 and periostin gene polymorphisms on serum periostin levels and cortical bone microstructure.

We investigated the interaction between periostin SNPs and the SNPs of the genes assumed to modulate serum periostin levels and bone microstructure in a cohort of postmenopausal women. We identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels and on radial cortical porosity. PURPOSE: The purpose of this study is to investigate the interaction between periostin gene polymorphisms (SNPs) and other genes potentially responsible for modulating serum periostin levels and bone microstructure in a cohort of postmenopausal women. METHODS: In 648 postmenopausal women from the Geneva Retirees Cohort, we analyzed 6 periostin SNPs and another 149 SNPs in 14 genes, namely BMP2, CTNNB1, ESR1, ESR2, LRP5, LRP6, PTH, SPTBN1, SOST, TGFb1, TNFRSF11A, TNFSF11, TNFRSF11B and WNT16. Volumetric BMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography at the distal radius and tibia. RESULTS: Serum periostin levels were associated with radial cortical porosity, including after adjustment for age, BMI, and years since menopause (p = 0.036). Sixteen SNPs in the ESR1, LRP5, TNFRSF11A, SOST, SPTBN1, TNFRSF11B and TNFSF11 genes were associated with serum periostin levels (p range 0.03-0.001) whereas 26 SNPs in 9 genes were associated with cortical porosity at the radius and/or at the tibia. WNT 16 was the gene with the highest number of SNPs associated with both trabecular and cortical microstructure. The periostin SNP rs9547970 was also associated with cortical porosity (p = 0.04). In particular, SNPs in LRP5, ESR1 and near the TNFRSF11A gene were associated with both cortical porosity and serum periostin levels. Eventually, we identified an interaction between LRP5 SNP rs648438 and periostin SNP rs9547970 on serum periostin levels (interaction p = 0.01) and on radial cortical porosity (interaction p = 0.005). CONCLUSION: These results suggest that periostin expression is genetically modulated, particularly by polymorphisms in the Wnt pathway, and is thereby implicated in the genetic variation of bone microstructure.

The role of calcium supplementation in healthy musculoskeletal ageing : An expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF).

The place of calcium supplementation, with or without concomitant vitamin D supplementation, has been much debated in terms of both efficacy and safety. There have been numerous trials and meta-analyses of supplementation for fracture reduction, and associations with risk of myocardial infarction have been suggested in recent years. In this report, the product of an expert consensus meeting of the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) and the International Foundation for Osteoporosis (IOF), we review the evidence for the value of calcium supplementation, with or without vitamin D supplementation, for healthy musculoskeletal ageing. We conclude that (1) calcium and vitamin D supplementation leads to a modest reduction in fracture risk, although population-level intervention has not been shown to be an effective public health strategy; (2) supplementation with calcium alone for fracture reduction is not supported by the literature; (3) side effects of calcium supplementation include renal stones and gastrointestinal symptoms; (4) vitamin D supplementation, rather than calcium supplementation, may reduce falls risk; and (5) assertions of increased cardiovascular risk consequent to calcium supplementation are not convincingly supported by current evidence. In conclusion, we recommend, on the basis of the current evidence, that calcium supplementation, with concomitant vitamin D supplementation, is supported for patients at high risk of calcium and vitamin D insufficiency, and in those who are receiving treatment for osteoporosis.

Occupation-dependent loading increases bone strength in men.

SUMMARY: Ex vivo analyses of humeri and radii from an anthropological collection and in vivo analyses of the distal radius of retired men indicate that occupation-dependent loading positively influences bone strength by an increase of bone size when young followed by a slowdown of the age-related endocortical and trabecular bone alteration. INTRODUCTION: Skeleton responds to mechanical stimuli, but it is not established whether chronic loading in the context of occupational activities (OA) influences bone properties. We assessed the impact of occupation-dependent loading on upper limb bone strength. METHODS: Individuals were classified according to the intensity of physical loading associated with their OA in two models. Ex vivo, computed tomography scans of the humeri and radii of 219 male skeletons (age of death, 20-93 years) from an anthropological collection of the 20th century (Simon collection) were used to determine estimates of bone strength and cross-sectional geometry. In vivo, distal radius were analysed in 180 men enrolled in the Geneva Retirees Cohort study using high-resolution peripheral quantitative computed tomography and finite element analysis. RESULTS: Heavy-loading OA was associated with higher bone strength in both models. This benefit was associated with higher total area (Tt.Ar), medullary area (Me.Ar) and cortical area (Ct.Ar) in young adult skeletons, but the difference decreased in older age. In older men, the humerus supporting heavy loading had a lower Me.Ar. This effect resulted in greater asymmetries of the Me.Ar and the Ct.Ar/Tt.Ar ratio between the humeri of men with unilateral versus bilateral heavy-loading OA. In vivo, an additional benefit of heavy-loading OA was observed on the distal radius trabecular density and microstructure. CONCLUSION: Repeated occupation-dependent loading positively influences bone strength by an increase of bone size when young followed by a slowdown of the age-related endocortical and trabecular bone alteration. These data supports the necessity to promote bone health in the context of sedentary occupation.

[Bone health in Geneva retirees]. / Santé osseuse des retraités genevois.

GERICO (Geneva Retirees Cohort) is a cohort of 953 men and women recruited at the age of 65 in Canton of Geneva, Switzerland, providing a picture of bone health at retirement time. Despite few comorbidities and good nutritional intake and vitamin D status, 30% of subjects have a history of vertebral or clinical fracture after the age of 45, 20% of women and 11% of men have osteoporosis assessed by DXA. 22% have a 10-year probability of a major osteoporotic fracture assessed by FRAX greater than 15%, -i.e. the current intervention thresholds recommended in this age-class in Switzerland. Nevertheless, only 1.4% subject benefits of an anti-osteoporotic drug. These data underscore the importance of primary and secondary prevention of osteoporosis and fractures in healthy elderly at time of retirement.

Additive Genetic Effects on Circulating Periostin Contribute to the Heritability of Bone Microstructure.

CONTEXT: Genetic factors account for 60-80% of the areal bone mineral density (aBMD) variance, whereas the heritability of bone microstructure is not clearly established. aBMD and microstructure are under the control of osteocytes, which regulate bone formation through the expression of molecules such as sclerostin (SOST) and periostin (POSTN). OBJECTIVE: We hypothesized that additive genetic effects contribute to serum levels of SOST and POSTN and thereby to the individual variance of bone microstructure. SUBJECTS AND METHODS: In a retrospective analysis of 432 subjects from the Geneva Retiree Cohort age 64.9 ± 1.4 years and 96 of their offspring age 37.9 ± 5.7 years, we measured serum SOST (sSOST) and serum POSTN (sPOSTN), distal radius and tibia microstructure, hip and lumbar spine aBMD, and bone turnover markers, Heritability (h(2), %) was calculated as twice the slope of the regression (ß) between parents and offspring. RESULTS: cPOSTN levels were significantly higher in men than women and in offspring than parents. h(2) values for bone microstructural traits ranged from 22-64% depending on the envelope (trabecular [Tb] or cortical [Ct]) and skeletal site (radius or tibia), whereas h(2) for sPOSTN and sSOST was 50% and 40%, respectively. sPOSTN was positively associated with Tb bone volume on total volume and Ct thickness, and negatively with Ct porosity. The associations for Ct parameters remain significant after adjustment for propetide of type-I procollagen, cross-linked telopeptide of type I collagen, femoral neck aBMD, sex or age. After adjustment of bone traits for sPOSTN, h(2) values decreased for several Tb and Ct bone parameters, but not for aBMD. In contrast, adjusting for sSOST did not alter h(2) values for bone traits. CONCLUSIONS: Additive genetic effects account for a substantial proportion of the individual variance of bone microstructure, sPOSTN, and sSOST. sPOSTN is largely inherited as a sex-related trait and carries an important contribution to the heritability of bone microstructure, indicating that these traits are at least partly determined by common genetic effects.

Prior ankle fractures in postmenopausal women are associated with low areal bone mineral density and bone microstructure alterations.

UNLABELLED: In a cross-sectional analysis in postmenopausal women, prior ankle fractures were associated with lower areal bone mineral density (BMD) and trabecular bone alterations compared to no fracture history. Compared to women with forearm fractures, microstructure alterations were of lower magnitude. These data suggest that ankle fractures are another manifestation of bone fragility. INTRODUCTION: Whether ankle fractures represent fragility fractures associated with low areal bone mineral density (aBMD) and volumetric bone mineral density (vBMD) and/or bone microstructure alterations remains unclear, in contrast to the well-recognised association between forearm fractures and osteoporosis. The objective of this study was to investigate aBMD, vBMD and bone microstructure in postmenopausal women with prior ankle fracture in adulthood, compared with women without prior fracture or with women with prior forearm fractures, considered as typically of osteoporotic origin. METHODS: In a cross-sectional analysis in the Geneva Retirees Cohort study, 63 women with ankle fracture and 59 with forearm fracture were compared to 433 women without fracture (mean age, 65 ± 1 years). aBMD was measured by dual-energy X-ray absorptiometry; distal radius and tibia vBMD and bone microstructure were measured by high-resolution peripheral quantitative computed tomography. RESULTS: Compared with women without fracture, those with ankle fractures had lower aBMD, radius vBMD (-7.9%), trabecular density (-10.7%), number (-7.3%) and thickness (-4.6%) and higher trabecular spacing (+14.5%) (P < 0.05 for all). Tibia trabecular variables were also altered. For 1 standard deviation decrease in total hip aBMD or radius trabecular density, odds ratios for ankle fractures were 2.2 and 1.6, respectively, vs 2.2 and 2.7 for forearm fracture, respectively (P ≤ 0.001 for all). Compared to women with forearm fractures, those with ankle fractures had similar spine and hip aBMD, but microstructure alterations of lower magnitude. CONCLUSION: Women with ankle fractures have lower aBMD and vBMD and trabecular bone alterations, suggesting that ankle fractures are another manifestation of bone fragility.

[Are bones in HIV-infected patient really fragile?]. / Les OS des personnes infectées par te VIH sont-ils si fragiles?

Impact of HIV infection on bone is now well established, with a high prevalence of osteoporosis and osteopenia and an increase of fracture risk, up to 5 fold for hip fractures. Beyond the usual risk factors frequently reported in this population, HIV infection itself and antiretroviral treatment, especially tenofovir, are involved in the pathophysiology of bone loss. Vitamin D deficiency is frequent and should be corrected. Fracture risk can be assessed based on clinical risk factors, the FRAX tool and bone mineral density measurement by DXA. Treatment in patients at increased risk of fracture is based on the same principles as in the general population, with mainly bisphosphonates.

[Osteoporosis in men]. / Osteoporose chez l'homme.

One man out of 5 experiences an osteoporotic fracture in his remaining lifetime at 50 years. Many comorbidities are associated with osteoporosis and fracture risk in men, with numerous associated risk factors beyond a decrease in bone mineral density (BMD), and also taking into account the risk of falling. A prevalent fragility fracture, oral glucocorticoid therapy for at least 3 months, and androgen deprivation therapy for prostate cancer are the three most common situations of increased risk of osteoporosis in men. Bisphosphonates, denosumab and teriparatide increase BMD and change bone turnover markers in the same magnitude as in women. The first anti-fracture data in men were obtained with zoledronic acid and denosumab.

Anorexia nervosa, osteoporosis and circulating leptin: the missing link.

UNLABELLED: Methods: Leptin levels were measured in 103 consecutive women with anorexia nervosa. Results: Spine BMD and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. INTRODUCTION: The purpose of this study was to assess leptin levels and other biological variables in a population of anorexia nervosa patients. METHODS: Leptin levels were measured consecutively in 103 women with anorexia nervosa (AN) with a mean age of 24.9 +/- 7.4 years. Osteodensitometry was also performed by dual energy X-ray absorptiometry (DXA). RESULTS: Spine bone mineral density (BMD) and Z-score values were found to be significantly lower in the low tertile compared with the highest tertile. Duration of amenorrhea and leptin level accounted for 27% of the variance in lumbar spine BMD. The mean leptin level was 3.9 +/- 4.6 ng/mL (normal values, 3.5-11 ng/mL). The distribution of leptin values was not a Gaussian distribution, and a log-transformed was therefore performed. A significant correlation was found between leptin level and spinal BMD (r = 0.3; p = 0.002); significant correlations were observed for both femoral neck and total hip BMDs. When leptin level values were divided into tertiles, spine BMD and Z-score values were found to be significantly lower in the lower tertile (p = 0.04 and p = 0.02) compared with the highest tertile. For femoral neck BMDs, the T-score was slightly lower between low and high tertile, but the difference was not statistically significant (p = 0.07). When multivariate analyses were performed, two independent factors which could possibly account for the variance in spinal BMDs were found. Duration of amenorrhea and leptin level accounted for 27% of the variance (p < 0.0001). CONCLUSION: The mechanisms underlying bone loss in AN patients remain unclear and complex, involving hypoestrogenia as well as nutritional factors such as insulin-like growth factor and leptin.