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.

[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.

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.

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.

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.

[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.

[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.

[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.

Effect of glucocorticoids on growth and bone mineral density in children with nephrotic syndrome.

UNLABELLED: Glucocorticosteroids (GCs) are the first-line treatment for idiopathic nephrotic syndrome (NS), but prolonged administration interferes with growth and bone mineralization. We conducted a retrospective study to analyze the long-term impact of prednisone on growth and bone mineral density (BMD) in children with NS. Data from children with NS followed during almost 10 years were analyzed. Height and spine BMD values were converted to Z-scores (standard deviation [SD]). The mean cumulative dose of GCs received was calculated and correlated to patient's growth and spine BMD using linear regression and subgroup analysis. We included 30 patients diagnosed at 3.7 years old (interquartile range (IQR) 2.6-4.8) and followed over 9.8 years (IQR 6.6-11.7). The one half of NS patients was steroid sensitive and one half dependent or resistant. The median cumulative dose of GCs received was 0.27 mg/kg/day (IQR 0.18-0.35). Growth and spine BMD were both negatively associated with the cumulative dose of GCs (P=0.001 and P=0.037, respectively). Final height Z-scores were significantly lower in patients receiving >0.2 mg/kg/day GCs (P=0.001). No difference was observed in spine BMD between subgroups. CONCLUSION: Increasing doses of GCs were significantly associated with lower height and BMD Z-scores. A significant effect on growth was observed with cutoff doses above 0.2 mg/kg/day.

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).

[Selective serotonin reuptake inhibitors (SSRI) and osteoporosis]. / Inhibiteurs sélectifs de la recapture de la sérotonine (ISRS) et ostéoporose.

Selective serotonin reuptake inhibitors (SSRI) represent the first-line treatment of depression. Several studies demonstrate that use of therapeutical doses of SSRI is associated with a decreased bone mineral density (BMD) and an increased risk of fracture. Mechanisms of action of SSRI on bone tissue are not totally clarified. These treatments would be associated with an increased risk of falls and would also have a direct effect on bone metabolism. Regarding proofs existing of the implication of SSRI on osteoporosis, while waiting for larger-scale prospective studies, it appears reasonable that practitioners assess bone loss within risk groups of patients treated with SSRI.

[General trend of hip fractures]. / Tendances séculaires des fractures de hanche.

Osteoporosis constitutes a major public health problem and hip fractures are a major cause of burden associated with osteoporosis in terms of mortality, disability, and costs. Since around 1990, a trend for a decrease of the age-adjusted incidence of hip fractures has been observed in western countries, particularly in women. In Geneva, with a confirmation at the Swiss level, a similar secular trend was observed. Nevertheless, due to the ageing of the population, this decrease of the incidence of hip fracture will probably not be sufficient to reduce the absolute number of these fractures over the next decades. Furthermore, age-adjusted hospitalizations in Switzerland for major non-hip osteoporotic fractures have continued to increase these last years.

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).

Older patients in the emergency department: a review.

Older patients account for up to a quarter of all emergency department (ED) visits. Atypical clinical presentation of illness, a high prevalence of cognitive disorders, and the presence of multiple comorbidities complicate their evaluation and management. Increased frailty, delayed diagnosis, and greater illness severity contribute to a higher risk of adverse outcomes. This article will review the most common conditions encountered in older patients, including delirium, dementia, falls, and polypharmacy, and suggest simple and efficient strategies for their evaluation and management. It will discuss age-related changes in the signs and symptoms of acute coronary events, abdominal pain, and infection, examine the yield of different diagnostic approaches in this population, and list the underlying medical problems present in half of all "social" admission cases. Complete geriatric assessments are time consuming and beyond the scope of most EDs. We propose a strategy based on the targeting of high-risk patients and provide examples of simple and efficient tools that are appropriate for ED use.

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.

The importance and relevance of peak bone mass in the prevalence of osteoporosis.

Bone mass and strength achieved at the end of the growth period, simply designated as 'Peak Bone Mass (PBM)', plays an essential role in the risk of osteoporotic fractures occurring in adulthood. It is considered that an increase of PBM by one standard deviation would reduce the fracture risk by 50%. As estimated from twin studies, genetics is the major determinant of PBM, accounting for about 60 to 80% of its variance. During pubertal maturation, the size of the bone increases whereas the volumetric bone mineral density remains constant in both genders. At the end of puberty, the sex difference is essentially due to a greater bone size in male than female subjects. This is achieved by larger periosteal deposition in boys, thus conferring at PBM a better resistance to mechanical forces in men than in women. Sex hormones and the IGF-1 system are implicated in the bone sexual dimorphism occurring during pubertal maturation. The genetically determined trajectory of bone mass development can be modulated to a certain extent by modifiable environmental factors, particularly physical activity, calcium and protein intakes. Prepuberty appears to be an opportune time to modify environmental factors that impinge on bone mineral mass acquisition.

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.

High-protein intake enhances the positive impact of physical activity on BMC in prepubertal boys.

UNLABELLED: In 232 healthy prepubertal boys, increased physical activity was associated with greater BMC at both axial and appendicular sites under high-protein intake. INTRODUCTION: Physical activity is an important lifestyle determinant of bone mineral mass acquisition. Its impact during childhood can be modulated by nutrition, particularly by protein and calcium intakes. We analyzed the relationship between physical activity levels and protein compared with calcium intake on BMC. MATERIALS AND METHODS: In 232 healthy prepubertal boys (age: 7.4 +/- 0.4 [SD] yr; standing height: 125.7 +/- 5.9 cm; body weight: 25.3 +/- 4.6 kg), physical activity and protein and calcium intakes were recorded. BMC was measured by DXA at the radial metaphysis, radial diaphysis, total radius, femoral neck, total hip, femoral diaphysis, and L(2)-L(4) vertebrae. RESULTS: In univariate analysis, the correlation coefficients r with BMC of the various skeletal sites were as follows: physical activity, from 0.26 (p = 0.0001) to 0.40 (p = 0.0001); protein intake, from 0.18 (p = 0.005) to 0.27 (p = 0.0001); calcium intake, from 0.09 (p = 0.181) to 0.17 (p = 0.007). By multiple regression analysis, the beta-adjusted values remained correlated with BMC, ranging as follows: physical activity, from 0.219 (p = 0.0007) to 0.340 (p < 0.0001); protein intake, from 0.120 (p = 0.146) to 0.217 (p = 0.009). In contrast, it was not correlated for calcium intake: from -0.069 (p = 0.410) to 0.001 (p = 0.986). With protein intake (mean = 2.0 g/kg body weight/d) above the median, increased physical activity from 168 to 321 kcal/d was associated with greater mean BMC Z-score (+0.6, p = 0.0005). In contrast with protein intake (mean = 1.5 g/kg body weight/d) below the median, increased physical activity from 167 to 312 kcal/d was not associated with a significantly greater mean BMC Z-score (+0.2, p = 0.371). The interaction between physical activity and protein intake was close to statistical significance for mean BMC Z-score (p = 0.055) and significant for femoral neck BMC (p = 0.012). In keeping with the results derived from multiple regression analysis, the increased physical activity on mean BMC Z-score was not influenced by difference in calcium intake above (mean = 945 mg/d) and below (mean = 555 mg/d) the median. CONCLUSION: In healthy prepubertal boys, the impact in increased physical activity on BMC seems to be enhanced by protein intake within limits above the usual recommended allowance.

Influence of age at menarche on forearm bone microstructure in healthy young women.

BACKGROUND: Shorter estrogen exposure from puberty onset to peak bone mass attainment may explain how late menarche is a risk factor for osteoporosis. The influence of menarcheal age (MENA) on peak bone mass, cortical, and trabecular microstructure was studied in 124 healthy women aged 20.4 +/- 0.6 (sd) yr. METHODS: At distal radius, areal bone mineral density (aBMD) was measured by dual-energy x-ray absorptiometry, and volumetric bone mineral density (BMD) and microstructure were measured by high-resolution peripheral computerized tomography, including: total, cortical, and trabecular volumetric BMD and fraction; trabecular number, thickness, and spacing; cortical thickness (CTh); and cross-sectional area (CSA). RESULTS: Median MENA was 12.9 yr. Mean aBMD T score of the whole cohort was slightly positive. aBMD was inversely correlated to MENA for total radius (R = -0.21; P = 0.018), diaphysis (R = -0.18; P = 0.043), and metaphysis (R = -0.19; P = 0.031). Subjects with MENA more than the median [LATER: 14.0 +/- 0.7 (+/-sd) yr] had lower aBMD than those with MENA less than the median (EARLIER: 12.1 +/- 0.7 yr) in total radius (P = 0.026), diaphysis (P = 0.042), and metaphysis (P = 0.046). LATER vs. EARLIER displayed lower total volumetric BMD (315 +/- 54 vs. 341 +/- 56 mg HA/cm(3); P = 0.010), cortical volumetric BMD (874 +/- 49 vs. 901 +/- 44 mg HA/cm(3); P = 0.003), and CTh (774 +/- 170 vs. 849 +/- 191 microm; P = 0.023). CTh was inversely related to CSA (R = -0.46; P < 0.001). In LATER reduced CTh was associated with 5% increased CSA. CONCLUSIONS: In healthy young adult women, a 1.9-yr difference in mean MENA was associated with lower radial aBMD T score, lower CTh without reduced CSA, a finding compatible with less endocortical accrual. It may explain how late menarche is a risk factor for forearm osteoporosis.