[Metabolic bone diseases : what's new in 2023]. / Maladies osseuses : ce qui a changé en 2023.

The sequential effects of romosozumab and denosumab in osteoporosis are shown in real-life, while the mechanisms of post-denosumab rebound are reviewed extensively. A network meta-analysis confirms the superiority of anabolics vs anti-resorptives on fracture reduction, while the latter shown a reduction of mortality in a large population-based study. Fracture risk prediction by FRAXPlus is improved. New meta-analyses confirm the benefits of Vitamin D on fractures and falls. Finally, multiples trials with new molecules for the treatment of rare bone diseases, including osteogenesis imperfecta, fibrous dysplasia and hypoparathyroidism, shown promising results.

Dans l'ostéoporose, les effets séquentiels du romosozumab et du dénosumab se précisent et les mécanismes du rebond à l'arrêt de ce dernier font l'objet d'une revue détaillée. Une méta-analyse en réseau confirme la supériorité des traitements anaboliques sur les antirésorbtifs, alors que l'effet de ces derniers sur la réduction de la mortalité est démontré dans une large étude populationnelle. La prédiction du risque fracturaire est améliorée par l'outil FRAXPlus. De nouvelles méta-analyses des bénéfices de la vitamine D sur le risque de fractures et de chutes sont également disponibles. Enfin, de nombreuses études encourageantes sur l'efficacité de nouveaux traitements dans de multiples maladies osseuse rares, telles l'ostéogenèse imparfaite, la dysplasie fibreuse et l'hypoparathyroïdie, ont été publiées.

Bone health: biology and nutrition.

PURPOSE OF REVIEW: Recent findings in the influence of dietary patterns, dairy products, beverages and microbiota composition and function on bone health are reviewed and discussed. RECENT FINDINGS: Evidence is accumulating on the increased risk of fracture in individuals following a vegan diet. Meta-analysis of randomized controlled trials indicates a favourable, though of low amplitude, effect of dairy products on bone mass accrual during childhood and adolescence. Though mostly based on results from observational studies, it seems that dairy product consumption, particularly fermented dairy products, is associated with a lower risk of hip fracture. Regular green tea drinkers may have a lower fracture risk than tea abstainers. Magnesium intake is beneficial for bone health. Prune supplements prevents bone loss in untreated postmenopausal women. This seems to be associated with modification of gut microbiota. SUMMARY: This information should help the medical practitioners facing questions from their patients on how to protect bone health through nutrition.

Functional brain changes in sarcopenia: evidence for differential central neural mechanisms in dynapenic older women.

BACKGROUND: The European Working Group on Sarcopenia in Older People (EWGSOP2) recently revised its definition and diagnostic criteria for sarcopenia, placing muscle strength at the forefront. The pathogenesis of dynapenia (or low muscle strength) is still not fully understood, but there is emerging evidence that central neural factors constitute critical determinants. METHODS: Our cross-sectional study included 59 community-dwelling older women (mean age 73.1 ± 4.9 years). Participants underwent detailed skeletal muscle assessments for muscle strength defined by handgrip strength and chair rise time measurements using the recently published EWGSOP2 cut-off points. Functional magnetic resonance imaging (fMRI) was assessed during the performance of a cognitive dual-task paradigm, consisting of a baseline, two single-tasks (motor and arithmetic) and one dual-task (motor and arithmetic combined). RESULTS: Forty-seven percent (28/59) of participants were classified as dynapenic. fMRI results revealed a differential recruitment of motor circuits in the brain during the dual-task condition in dynapenic as compared with non-dynapenic participants. In particular, while the brain activity during the single-tasks did not differ between the two groups, only during the dual-task non-dynapenic participants showed significant increased activation in dorsolateral prefrontal and premotor cortex, and in supplementary motor area as compared to dynapenic participants. CONCLUSION: Our results point to a dysfunctional involvement of brain networks associated with motor control in dynapenia in a multi-tasking paradigm. A better knowledge of the link between dynapenia and brain functions could provide new impulses in the diagnosis and interventions for sarcopenia.

Role of vitamin D supplementation in the management of musculoskeletal diseases: update from an European Society of Clinical and Economical Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group.

Vitamin D is a key component for optimal growth and for calcium-phosphate homeostasis. Skin photosynthesis is the main source of vitamin D. Limited sun exposure and insufficient dietary vitamin D supply justify vitamin D supplementation in certain age groups. In older adults, recommended doses for vitamin D supplementation vary between 200 and 2000 IU/day, to achieve a goal of circulating 25-hydroxyvitamin D (calcifediol) of at least 50 nmol/L. The target level depends on the population being supplemented, the assessed system, and the outcome. Several recent large randomized trials with oral vitamin D regimens varying between 2000 and 100,000 IU/month and mostly conducted in vitamin D-replete and healthy individuals have failed to detect any efficacy of these approaches for the prevention of fracture and falls. Considering the well-recognized major musculoskeletal disorders associated with severe vitamin D deficiency and taking into account a possible biphasic effects of vitamin D on fracture and fall risks, an European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO) working group convened, carefully reviewed, and analyzed the meta-analyses of randomized controlled trials on the effects of vitamin D on fracture risk, falls or osteoarthritis, and came to the conclusion that 1000 IU daily should be recommended in patients at increased risk of vitamin D deficiency. The group also addressed the identification of patients possibly benefitting from a vitamin D loading dose to achieve early 25-hydroxyvitamin D therapeutic level or from calcifediol administration.

Prevalence of Low Serum Alkaline Phosphatase and Hypophosphatasia in Adult Patients with Atypical Femur Fractures.

Hypophosphatasia (HPP) is a rare genetic disorder characterized by low serum alkaline phosphatase (ALP), its manifestations may include atypical femoral fractures (AFF). However, the prevalence of low serum ALP and HPP in patients with AFF remains unknown. We retrospectively analyzed ALP levels and clinical manifestations compatible with HPP in 72 adult patients with confirmed AFF by chart review. ALP values were compared with those of a control group of patients with prior proximal femoral fracture during antiresorptive treatment (n = 20). Among the AFF patients, 18 (25%) had at least one serum ALP value ≤ 40 IU/L, although in all but one case, at least one ALP value > 40 IU/L was also detected at another time point. Most low ALP values were associated with antiresorptive treatment (P = 0.049) and lowest levels of ALP did not differ between the AFF and the control groups (P = 0.129). However, low ALP values among AFF patients were associated with a higher rate of bilateral AFF (50% vs 22%, P = 0.025), metatarsal fracture (33% vs 7%, P = 0.006), and with trends for more frequent use of glucocorticoid (22% vs 8%, P = 0.089) and proton pump inhibitor (61% vs 44%, P = 0.220). In one AFF patient with low ALP and clinical suspicion of HPP, a rare pathogenic heterozygous variant of the ALPL gene was identified. In conclusion, low ALP values are common among subjects with AFF and mainly related to concomitant antiresorptive medication. Hence, low serum ALP has low specificity for HPP among AFF patients.

Acquisition of peak bone mass.

Peak bone mass (PBM) is a key determinant of bone mass and fragility fractures later in life. The increase in bone mass during childhood and adolescence is mainly related to an increase in bone size rather to changes in volumetric bone density. Race, gender, and genetic factors are the main determinants of PBM achievement. Nevertheless, environmental factors such as physical activity, calcium and protein intakes, weight and age at menarche, are also playing an important role in bone mass accrual during growth. Therefore, optimization of calcium and protein intakes and weight-bearing physical activity during growth is an important strategy for optimal acquisition of PBM and bone strength and for contributing to prevent fractures later in life.

Fracture Risk Following an Atypical Femoral Fracture.

Atypical femoral fractures (AFFs) occurring during the course of osteoporosis treatment usually lead to discontinuation of anti-resorptive (AR) drugs. However, the risk of fracture after an AFF is unknown. We conducted a follow-up study of patients with AFF matched 1:3 for age and gender with patients with a peripheral major osteoporotic fracture (pMOF), in the setting of a fracture liaison service, to investigate the incidence of subsequent low-trauma fractures. Fifty-five patients with AFF (95% women, age [mean ± standard deviation] 75 ± 10 years, 89% exposed to AR drugs), followed for 6.2 ± 3.7 years, were compared to 165 matched controls with a pMOF (hip 85%) followed for 4.3 ± 2.6 years. During the follow-up, 38% of patients in the AFF group and 16% in the pMOF group received AR therapies. Continuation of AR drugs after an AFF was associated with contralateral AFF in 27% of subjects. The risks of new low-trauma, major osteoporotic and imminent (within 2 years) fractures, were similar between the two groups: incidence rate ratio (95% confidence interval [CI]) of subsequent fracture following AFF relative to pMOF, 1.30 (95% CI, 0.82-2.04), 1.28 (95% CI, 0.74-2.15), and 1.11 (95% CI, 0.54-2.15), respectively. Moreover, the risk of sustaining multiple fractures per participant was significantly increased among patients with AFF compared to pMOF (hazard ratio 1.48 [95% CI, 1.00-2.19]; p = 0.049). When taking mortality into account, the risk of subsequent fractures tended to be higher in the AFF group (sub-hazard ratio 1.42 [95% CI, 0.95-2.12]). In conclusion, patients who sustained an AFF are at high risk of subsequent fragility fractures, at least equal or even greater to the risk observed after a pMOF. However, continuation of AR drugs increases the risk of contralateral AFF. Therefore, optimal modalities for secondary fracture prevention after AFF require further evaluation. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

[Development and evaluation of Fracture Liaison Service in Switzerland]. / Développement et évaluation des filières de l'ostéoporose en Suisse.

Osteoporosis is a major public health problem linked to fractures and more particularly to those of the hip, which is the major complication in terms of morbidity, mortality and costs. As the risk of a new fragility fracture is greatly increased after a first fracture episode, the concept of the « Osteoporosis pathway ¼ or « Fracture Liaison Service ¼, led by an interdisciplinary team with a coordinator, was developed for the secondary prevention of fractures. Osteoporosis pathways for which key performance indicators have recently been described, have demonstrated their ability to reduce the incidence of new fractures with a favorable cost-effectiveness ratio. Over the past two years, the development of the osteoporosis pathways network in Switzerland has been the main initiative led by the Swiss Association against Osteoporosis.

L'ostéoporose est un problème majeur de santé publique en lien avec les fractures, et plus particulièrement avec la fracture de la hanche qui est la complication principale en termes de morbidité, de mortalité et de coûts. Le risque de nouvelle fracture de fragilité étant fortement augmenté après une première fracture, le concept de « Filière ostéoporose ¼ ou « Fracture Liaison Service ¼, animée par une équipe interdisciplinaire avec un coordinateur, a été développé pour la prévention secondaire des fractures. Les filières ostéoporose, pour lesquelles des indicateurs clés de performance ont été récemment décrits, ont démontré leur capacité à réduire l'incidence de nouvelles fractures avec un rapport coût-efficacité favorable. Au cours de ces deux dernières années, le développement du réseau de filières ostéoporose en Suisse a été la principale initiative menée par l'Association suisse contre l'ostéoporose.

A Novel HR-pQCT Image Registration Approach Reveals Sex-Specific Changes in Cortical Bone Retraction With Aging.

During aging, changes in endosteal and periosteal boundaries of cortical bone occur that differ between men and women. We here develop a new procedure that uses high-resolution peripheral quantitative CT (HR-pQCT) imaging and 3D registration to identify such changes within the timescale of longitudinal studies. A first goal was to test the sensitivity of the approach. A second goal was to assess differences in periosteal/endosteal expansion over time between men and women. Rigid 3D registration was used to transform baseline and all follow-up (FU) images to a common reference configuration for which the region consisting of complete slices (largest common height) was determined. Periosteal and endosteal contours were transformed to the reference position to determine the net periosteal and endosteal expansion distances. To test the sensitivity, images from a short-term reproducibility study were used (15 female, aged 21 to 47 years, scanned three times). To test differences between men and women, images from a subset of the Geneva Retirees Cohort were used (248 female, 61 male, average age 65 years, 3.5 and 7 years FU). The sensitivity study indicated a least significant change for detecting periosteal/endosteal expansion of 41/31 microns for the radius and 17/26 microns for the tibia. Results of the cohort study showed significant net endosteal retraction only in females at the radius and tibia after 3.5 years (38.0 and 38.4 microns, respectively) that further increased at 7 years FU (70.4 and 70.8 microns, respectively). No significant net periosteal changes were found for males or females at 7 years. The results demonstrate that it is possible to measure changes in endosteal contours in longitudinal studies within several years. For the investigated cohort, significant endosteal retraction was found in females but not in males. Whether these changes in cortical geometry are related to fracture risk remains to be investigated in larger cohorts © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Associations between age-related changes in bone microstructure and strength and dietary acid load in a cohort of community-dwelling, healthy men and postmenopausal women.

BACKGROUND: The importance of dietary acid load (DAL) in the pathogenesis of osteoporosis is still debated. Age-related changes in bone microstructure and strength in relation to DAL remain largely unexplored. OBJECTIVES: We investigated the associations between changes in areal and volumetric bone mineral density (BMD), bone microstructure and strength, fracture risk, and DAL in a prospective cohort of 65-y-old healthy men and postmenopausal women. METHODS: Potential renal acid load (PRAL; mEq/d) was calculated as a DAL proxy to characterize participants' diet as alkaline (Alk-D; PRAL < -5), neutral (Neut-D; -5 ≤ PRAL ≤ 5), or acidic (Acid-D; PRAL >5). We measured areal BMD (aBMD) by DXA, and distal radius and tibia bone microstructure using high-resolution peripheral quantitative computed tomography, at baseline (n = 853) and after 6.1 ± 1.4 y (n = 708). Bone strength was estimated using finite element analyses at baseline and after 3.0 ± 0.5 y (n = 613). Prevalent and incident fractures were recorded. RESULTS: The majority of the participants (59%) had an Alk-D, while 23% had a Neut-D, and 18% an Acid-D. Baseline aBMD and bone microstructure and strength did differ or were slightly better in women or men with an Acid-D versus those consuming an Alk-D or Neut-D. Indeed, women with an Acid-D had higher trabecular number (P = 0.010 vs. Alk-D; P = 0.001 vs. Neut-D), while men had higher hip and radius aBMD (P = 0.008 and 0.024 vs. Neut-D, respectively) and radius strength (P = 0.026 vs. Neut-D). Over the follow-up, women in the Acid-D group experienced lower cortical and endocortical bone loss at the radius than did the Alk-D and Neut-D groups (cortical thickness, P = 0.008 and < 0.001; trabecular area, P = 0.001 and < 0.001, respectively). No association between fractures and PRAL was observed. CONCLUSIONS: These null or favourable associations between baseline values or changes in aBMD, bone microstructure and strength, and DAL in this cohort of 65-y-old healthy individuals do not support adverse DAL-mediated effects on bone. This trial was registered at http://www.isrctn.com as ISRCTN11865958.

[Multiple myeloma in the elderly†: impact of a geriatric assessment]. / Le myélome multiple chez la personne âgée†: impact d'une évaluation gériatrique.

Multiple myeloma (MM) is the third most common hematological cancer. MM is a proliferation of plasma cells Its incidence increases from 1 per 100 000 at 40 years to 40 per 100 000 at 80 years. Today, there are many treatment strategies for MM that go from simple care to self-transplantation. Choosing the most appropriate treatment can be challenging in geriatric patients. This population is heterogeneous and therapeutic decisions shouldn't be based on an age limit. Therefore, geriatric assessment is essential to help the clinician choose the best therapeutic strategy and assess the patient's specific needs.

Le myélome multiple (MM) est le troisième cancer hématologique le plus fréquent. Le MM est une prolifération de plasmocytes. Son incidence passe de moins de 1 pour 100 000 à 40 ans, à 40 pour 100 000 à 80 ans. Aujourd'hui, il existe de nombreuses lignes de traitement pour le MM, qui vont de simples soins d'accompagnement à l'autogreffe. La décision quant à la meilleure thérapie peut s'avérer délicate au sein de la population gériatrique. En effet, cette population est hétérogène et il est risqué de baser la décision thérapeutique sur une limite d'âge. L'évaluation gériatrique est donc fondamentale, car elle permet de catégoriser le patient afin d'aider le clinicien à choisir la meilleure stratégie thérapeutique et d'évaluer les besoins spécifiques du patient.

[Orthogeriatric care†: what specificities†?] / Prise en charge orthogériatrique†: quelles spécificités†?

Hip fracture in the elderly is associated with an increase in disability and mortality. Early intervention programs accelerate the recovery period and reduce mortality. The intervention of geriatricians, with direct responsibility during the acute phase, has demonstrated an optimal benefit, as well as joint management by a geriatrician and an orthopedist. Recruiting motivated patients, able to walk with or without help before the fracture and regardless of their cognitive level, ensures successful intervention and reduced costs. The most effective interventions are those aimed at recovery of activities of daily living, with occupational therapy and muscle training. Correction of protein and vitamin intake also has a significant effect on the patient's progress in rehabilitation.

La fracture de hanche chez la personne âgée est associée avec une augmentation du handicap et de la mortalité. Les programmes d'intervention précoce accélèrent la période de récupération et réduisent la mortalité. L'intervention des gériatres, avec une responsabilité directe durant la phase aiguë, a démontré un bénéfice optimal, de même que la prise en charge conjointe par un gériatre et un orthopédiste. Le recrutement de patients motivés, capables de marcher avec ou sans aide avant la fracture et indépendamment de leur niveau cognitif, assure le succès de l'intervention et une réduction des coûts. Les interventions les plus efficaces sont celles qui visent une récupération des activités de la vie quotidienne, avec une thérapie occupationnelle et un entraînement musculaire. La correction de l'apport protéique et vitaminique a aussi un effet significatif sur l'évolution du patient en réhabilitation.

Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study.

BACKGROUND: Although areal bone mineral density (aBMD) assessed by dual-energy x-ray absorptiometry (DXA) is the clinical standard for determining fracture risk, most older adults who sustain a fracture have T scores greater than -2·5 and thus do not meet the clinical criteria for osteoporosis. Importantly, bone fragility is due to low BMD and deterioration in bone structure. We assessed whether indices of high-resolution peripheral quantitative CT (HR-pQCT) were associated with fracture risk independently of femoral neck aBMD and the Fracture Risk Assessment Tool (FRAX) score. METHODS: We assessed participants in eight cohorts from the USA (Framingham, Mayo Clinic), France (QUALYOR, STRAMBO, OFELY), Switzerland (GERICO), Canada (CaMos), and Sweden (MrOS). We used Cox proportional hazard ratios (HRs) to estimate the association between HR-pQCT bone indices (per 1 SD of deficit) and incident fracture, adjusting for age, sex, height, weight, and cohort, and then additionally for femoral neck DXA aBMD or FRAX. FINDINGS: 7254 individuals (66% women and 34% men) were assessed. Mean baseline age was 69 years (SD 9, range 40-96). Over a mean follow-up of 4·63 years (SD 2·41) years, 765 (11%) participants had incident fractures, of whom 633 (86%) had femoral neck T scores greater than -2·5. After adjustment for age, sex, cohort, height, and weight, peripheral skeleton failure load had the greatest association with risk of fracture: tibia HR 2·40 (95% CI 1·98-2·91) and radius 2·13 (1·77-2·56) per 1 SD decrease. HRs for other bone indices ranged from 1·12 (95% CI 1·03-1·23) per 1 SD increase in tibia cortical porosity to 1·58 (1·45-1·72) per 1 SD decrease in radius trabecular volumetric bone density. After further adjustment for femoral neck aBMD or FRAX score, the associations were reduced but remained significant for most bone parameters. A model including cortical volumetric bone density, trabecular number, and trabecular thickness at the distal radius and a model including these indices plus cortical area at the tibia were the best predictors of fracture. INTERPRETATION: HR-pQCT indices and failure load improved prediction of fracture beyond femoral neck aBMD or FRAX scores alone. Our findings from a large international cohort of men and women support previous reports that deficits in trabecular and cortical bone density and structure independently contribute to fracture risk. These measurements and morphological assessment of the peripheral skeleton might improve identification of people at the highest risk of fracture. FUNDING: National Institutes of Health National Institute of Arthritis Musculoskeletal and Skin Diseases.

Evaluation of Radius Microstructure and Areal Bone Mineral Density Improves Fracture Prediction in Postmenopausal Women.

A majority of low-trauma fractures occur in subjects with only moderate decrease of areal bone mineral density (aBMD), ie, osteopenia, assessed by dual-energy X-ray absorptiometry (DXA) or low fracture probability assessed by FRAX. We investigated whether peripheral bone microstructure and estimated strength improve the prediction of incident fractures beyond central DXA and FRAX. In this population-based study of 740 postmenopausal women (aged 65.0 ± 1.4 years) from the Geneva Retirees Cohort (ISRCTN registry 11865958), we assessed at baseline cortical (Ct) and trabecular (Tb) volumetric bone mineral density (vBMD) and microstructure by peripheral quantitative computed tomography (HR-pQCT); bone strength by micro-finite element analysis; aBMD and trabecular bone score (TBS) by DXA; and FRAX fracture probability. Eighty-five low-trauma fractures occurred in 68 women over a follow-up of 5.0 ± 1.8 years. Tb and Ct vBMD and microstructure predicted incident fractures, independently of each other and of femoral neck (FN) aBMD and FRAX (with BMD ± TBS). However, the associations were markedly attenuated after adjustment for ultra-distal radius aBMD (same bone site). The best discrimination between women with and without fracture was obtained at the radius with total vBMD, the combination of a Tb with a Ct parameter, or with failure load, which improved the area under the curve (AUC) for major osteoporotic fracture when added to FN aBMD (0.760 versus 0.695, p = 0.022) or to FRAX-BMD (0.759 versus 0.714, p = 0.015). The replacement of failure load by ultra-distal aBMD did not significantly decrease the AUC (0.753, p = 0.747 and 0.750, p = 0.509, respectively). In conclusion, peripheral bone microstructure and strength improve the prediction of fractures beyond central DXA and FRAX but are partially captured in aBMD measured by DXA at the radius. Because HR-pQCT is not widely available for clinical purposes, assessment of ultra-distal radius aBMD by DXA may meanwhile improve fracture risk estimation. © 2017 American Society for Bone and Mineral Research.

Serum Levels of a Cathepsin-K Generated Periostin Fragment Predict Incident Low-Trauma Fractures in Postmenopausal Women Independently of BMD and FRAX.

Periostin is a matricellular protein involved in bone formation and bone matrix organization, but it is also produced by other tissues. Its circulating levels have been weakly associated with bone microstructure and prevalent fractures, possibly because periostin measured by the current commercial assays does not specifically reflect bone metabolism. In this context, we developed a new ELISA for a periostin fragment resulting from cathepsin K digestion (K-Postn). We hypothesized that circulating K-Postn levels could be associated with bone fragility. A total of 695 women (age 65.0 ± 1.5 years), enrolled in the Geneva Retirees Cohort (GERICO), were prospectively evaluated over 4.7 ± 1.9 years for the occurrence of low-trauma fractures. At baseline, we measured serum periostin, K-Postn, and bone turnover markers (BTMs), distal radius and tibia microstructure by HR-pQCT, hip and lumbar spine aBMD by DXA, and estimated fracture probability using the Fracture Risk Assessment Tool (FRAX). Sixty-six women sustained a low-trauma clinical fracture during the follow-up. Total periostin was not associated with fractures (HR [95% CI] per SD: 1.19 [0.89 to 1.59], p = 0.24). In contrast, K-Postn was significantly higher in the fracture versus nonfracture group (57.5 ± 36.6 ng/mL versus 42.5 ± 23.4 ng/mL, p < 0.001) and associated with fracture risk (HR [95%CI] per SD: 2.14 [1.54 to 2.97], p < 0.001). After adjustment for aBMD, FRAX, bone microstructure, or BTMs, K-Postn remained significantly associated with fracture risk. The performance of the fracture prediction models was improved by adding K-Postn to aBMD or FRAX (Harrell C index for fracture: 0.70 for aBMD + K-Post versus 0.58 for aBMD alone, p = 0.001; 0.73 for FRAX + K-Postn versus 0.65 for FRAX alone, p = 0.005). Circulating K-Postn predicts incident fractures independently of BMD, BTMs, and FRAX in postmenopausal women. Hence measurement of a periostin fragment resulting from in vivo cathepsin K digestion may help to identify subjects at high risk of fracture. © 2017 American Society for Bone and Mineral Research.

Structural Basis of Bone Fragility in Young Subjects with Inflammatory Bowel Disease: A High-resolution pQCT Study of the SWISS IBD Cohort (SIBDC).

BACKGROUND: The onset of inflammatory bowel disease (IBD) during childhood/adolescence compromises peak bone mass acquisition and predisposes to fractures later in life. However, the structural basis for bone fragility in young adults with IBD remains unknown. METHODS: One hundred two young subjects from the Swiss IBD cohort were included. Areal bone mineral density (aBMD) at distal radius, hip, and spine as well as morphometric vertebral fractures were assessed using dual-energy x-ray absorptiometry technique. Volumetric (v)BMD, trabecular, and cortical bone microstructure at the distal radius and tibia were assessed by high-resolution peripheral quantitative computed tomography. Areal, vBMD, and microstructure were compared between patients with IBD and healthy matched controls (n = 389). Multiple regression analysis was used to evaluate variables associated with bone microarchitecture and fractures. RESULTS: Clinical fractures were reported in 37 IBD subjects (mean age 23 yrs), mostly of the forearm; 5 subjects had morphometric vertebral fractures. After adjusting for age, sex, and height, tibia trabecular (Tb)vBMD, thickness, and distribution were significantly associated with fractures, whereas aBMD was not. After adjusting for aBMD, radius Tb distribution and tibia (Tb)vBMD and trabecular thickness still remained associated with fractures. Compared with healthy controls, patients with IBD had significantly lower aBMD at all sites, as well as alteration in (Tb)vBMD and trabecular microstructure at the distal radius and tibia, and these alterations were correlated with disease severity. CONCLUSIONS: Young patients with IBD have low aBMD and altered trabecular bone microarchitecture compared with healthy controls. The latter is independently associated with fractures and may predispose increased susceptibility to fragility fractures throughout life.

Fracture Prospectively Recorded From Prepuberty to Young Adulthood: Are They Markers of Peak Bone Mass and Strength in Males?

Fractures are common in otherwise healthy children and adolescents. They result from trauma of varying severity. Some reflect a greater skeletal fragility. A long-term implication of these fractures is their potentiality to predict adult bone fragility and increased risk of osteoporosis in later life. Using dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and micro-finite element analysis (µFEA) measurements, we previously found in 124 healthy females, followed from the age of 7.9 to 20.4 years, substantial deficits in both structural and strength components of the radius in the 42 girls who sustained a fracture during skeletal development. The objective of the current study was to assess in healthy males the relationship between fracture during development and expression of bone fragility in adulthood. A cohort of 152 boys was followed from age 7.4 ± 04 (mean ± SD) to 22.6 ± 0.7 years, ie, when peak bone mass is attained. Ninety participants (59.2%) sustained at least one fracture during growth, with highest incidence within the 10- to 13-year age range. Forearm was the most frequent site of fractures. At 7.4 years, several bone DXA-measured variables (areal bone mineral density [aBMD], bone mineral content [BMC]) were lower in the group with a positive fracture history during skeletal development compared with the non-fractured group. In contrast, at 22.6 years, no DXA-measured sites, including forearm, indicated a deficit in the fractured group compared with the non-fractured group. Likewise, at 22.6 years, neither HR-pQCT nor µFEA measurements, including distal radius, showed a structural or strength deficit in the fractured group. These results markedly contrast with a similar prospective study using the same technical and clinical design in 124 healthy girls. In conclusion, our prospective studies suggest a sex difference in the predictability of bone fragility in young adults who sustained fractures during childhood and adolescence. This difference might be related to the degree of trauma severity, usually lower in girls than in boys. © 2017 American Society for Bone and Mineral Research.

Peripheral skeleton bone strength is positively correlated with total and dairy protein intakes in healthy postmenopausal women.

BACKGROUND: Bone mineral content (BMC) and bone mineral density (BMD) are positively correlated with dietary protein intakes, which account for 1-8% of BMC and BMD variances. However, the relation between bone strength and microstructure, which are variables that are not captured by areal bone mineral density (aBMD), and dietary protein intakes, particularly from specific dietary sources, has not been clearly established. OBJECTIVE: We investigated the association between the peripheral skeleton-predicted failure load and stiffness, bone microstructure, and dietary protein intakes from various origins (animal, divided into dairy and nondairy, and vegetable origins) in healthy postmenopausal women. DESIGN: In a cross-sectional study in 746 Caucasian women aged 65.0 ± 1.4 y, we measured the aBMD with the use of dual-energy X-ray absorptiometry, the distal radius and tibia bone microstructures with the use of high-resolution peripheral quantitative computerized tomography, and bone strength with the use of a finite element analysis, and we evaluated dietary protein and calcium with the use of a validated food-frequency questionnaire. RESULTS: Mean dietary calcium and protein intakes were greater than recommended amounts for this class of age. The predicted failure load and stiffness at the distal radius and tibia were positively associated with total, animal, and dairy protein intakes but not with vegetable protein intake. Failure load differences were accompanied by modifications of the aBMD and of cortical and trabecular bone microstructures. The associations remained statistically significant after adjustment for weight, height, physical activity, menopause duration, calcium intake, and the interaction between calcium and protein intake. A principal component analysis of the volumetric BMD and bone microstructure indicated that trabecular bone mainly contributed to the positive association between protein intakes and bone strength. CONCLUSIONS: These results, which were recorded in a very homogeneous population of healthy postmenopausal women, indicate that there is a beneficial effect of animal and dairy protein intakes on bone strength and microstructure. Specifically, there is a positive association between the bone failure load and stiffness of the peripheral skeleton and dietary protein intake, which is mainly related to changes in the trabecular microstructure. This trial was registered at www.controlled-trials.com as ISRCTN11865958.

Prepubertal Impact of Protein Intake and Physical Activity on Weight-Bearing Peak Bone Mass and Strength in Males.

Context: Peak bone mass (PBM) and strength are important determinants of fracture risk in later life. During growth, bone is responsive to changes in nutrition and physical activity (PA), particularly before pubertal maturation. Objective: In prepubertal healthy boys, protein intake (Prot-Int) enhances the impact of PA on weight-bearing bone. We hypothesized that the synergism between Prot-Int and PA on proximal femur as recorded at 7.4 years would track until PBM. Methods: A total of 124 boys were followed from 7.4 to 15.2 and 22.6 years. At 7.4 years, they were dichotomized according to the median of both PA and Prot-Int. Results: In boys with PA greater than the median (310 vs 169 kcal ⋅ d-1), higher vs low Prot-Int (57.7 vs 38.0 g ⋅ d-1) was associated with +9.8% greater femoral neck (FN) bone mineral content (BMC) (P = 0.027) at 7.4 years. At 15.2 and 22.6 years, this difference was maintained: FN BMC: +12.7% (P = 0.012) and +11.3% (P = 0.016), respectively. With PA greater than the median, in Prot-Int greater than vs less than the median, differences in FN BMC z scores were +0.60, +0.70, and +0.68 at 7.4, 15.2, and 22.6 years, respectively. Microfinite element analysis of distal tibia at 15.2 and 22.6 years indicated that in the 2 groups with PA greater than the median, cross-sectional area, stiffness, and failure load were greater in Prot-Int greater than vs less than the median. Conclusions: This study demonstrates the crucial influence of Prot-Int on the response to enhanced PA and the importance of prepubertal years for modifying the bone growth trajectory and, thereby, for achieving higher PBM and greater strength in healthy male participants.

Within- and Across-Sex Inheritance of Bone Microarchitecture.

Context: The maternal heritability of bone microarchitecture according to the sex of the offspring is not known. Objective: To explore sex difference and influence of mother's menopausal status on the heritability of bone microarchitecture between mothers and their offspring. Subjects and Methods: In 102 mother-daughter and 161 mother-son pairs, volumetric bone mineral density (BMD) and bone microarchitecture were measured at the distal radius and tibia by high-resolution peripheral quantitative computed tomography. A principal components analysis was applied for the radius and the tibia volumetric BMD and microarchitecture parameters separately. Two components, a trabecular one and a cortical one were identified at the radius and tibia. Half heritability (½h2) was estimated as the slope of the regression between offspring and mothers for each bone parameter separately. Results: The mean age (± standard deviation) of mothers and daughters was 50.6 ± 4.1 years and 20.4 ± 0.5 years, respectively; that of mothers and sons was 45.8 ± 3.9 years and 15.2 ± 0.5 years, respectively. Most trabecular and cortical parameters were inherited in both mother-daughter and mother-son pairs (ß = 0.15 to 0.33; P = 0.05 to 0.001). At the tibia, trabecular and cortical principal components were significantly inherited in both sexes, whereas only the trabecular one was inherited at the radius (½h2, 21% to 35%). There was no difference in heritability of bone microarchitecture between mother-daughter and mother-son pairs. All heritabilities remained after adjustment for age, weight, height, gonadal status, and areal BMD (½h2, 9% to 25%). In the mother-daughter pairs, there was no systematic drop of heritability across menopause. Conclusions: Volumetric bone density and microarchitecture are highly and similarly inherited between and within sexes. The genetic effects remain predominant across menopause.