Dual-energy X-ray absorptiometric bone mineral density (DXA BMD) is a strong predictor of fracture risk in untreated patients. However, previous patient-level studies suggest that BMD changes explain little of the fracture risk reduction observed with osteoporosis treatment. We investigated the relevance of DXA BMD changes as a predictor for fracture risk reduction using data from the FREEDOM trial, which randomly assigned placebo or denosumab 60 mg every 6 months to 7808 women aged 60 to 90 years with a spine or total hip BMD T-score < −2.5 and not < −4.0. We took a standard approach to estimate the percent of treatment effect explained using percent changes in BMD at a single visit (months 12, 24, or 36). We also applied a novel approach using estimated percent changes in BMD from baseline at the time of fracture occurrence (time-dependent models). Denosumab significantly increased total hip BMD by 3.2%, 4.4%, and 5.0% at 12, 24, and 36 months, respectively. Denosumab decreased the risk of new vertebral fractures by 68% (p < 0.0001) and nonvertebral fracture by 20% (p = 0.01) over 36 months. Regardless of the method used, the change in total hip BMD explained a considerable proportion of the effect of denosumab in reducing new or worsening vertebral fracture risk (35% [95% confidence interval (CI): 20%–61%] and 51% [95% CI: 39%–66%] accounted for by percent change at month 36 and change in time-dependent BMD, respectively) and explained a considerable amount of the reduction in nonvertebral fracture risk (87% [95% CI: 35% – >100%] and 72% [95% CI: 24% – >100%], respectively). Previous patient-level studies may have underestimated the strength of the relationship between BMD change and the effect of treatment on fracture risk or this relationship may be unique to denosumab. © 2012 American Society for Bone and Mineral Research

The total skeletal bone mineral content (BMC), bone mineral density (BMD), bone size, and body composition were measured by dual-energy x-ray absorptiometry (DXA) in all professional male football players of a 1st division team (n = 24) and age- and BMI-matched (n = 22) controls (less than 3 hours of recreational sport activities per week). Average (+/- 1 SD) age of the athletes was 22.6 +/- 2.5 years. Intensive training is conducted during 48 weeks a year for 20-22 hours/week. The length of the registered playing career before the study was 8.2 +/- 2.7 years. Total skeleton BMC was 18.0% (P < 0.001) greater in the football players. The difference resulted from the sum of 5.2% (P < 0.02) increment of bone size and 12.3% (P < 0.001) increment of BMD. The analysis of skeletal subareas revealed that the difference of the BMC and BMD was greater at the level of the pelvis and legs compared with the arms or trunk. The BMC and BMD of the head was equal for both groups. Also, the bone size of the legs and pelvis was significantly greater for the players compared with controls; there was no difference at the level of the arms or head. Within the group of football players the increment of total skeleton BMD was similar in the young players, with less than 7 years of practice (age 20.6 +/- 0.9 years) compared with relative older players (age 24.6 +/- 1.9) with more than 7 years of practice. Lean body mass was significantly greater in the players (63.3 +/- 4.0 kg) compared with the controls (56.7 +/- 3.6, P < 0.001) whereas fat mass was markedly lower (9.4 +/- 2.9 kg versus 14.9 +/- 6.3 kg), P < 0.002). The BMD of the controls was significantly correlated to total weight, height, and lean mass whereas the BMD of the players was only correlated to muscle mass. The calcium intake from dairy products was similar in both groups. The range of calcium intake was wide among the players (184-2519 mg/day) but it was not significantly correlated to BMD (r = 0.03). In conclusion, male professional football players develop a significant increment of BMC as a result of increased bone size and density. This is already present at the end of the second decade and maintained at least to the end of the third decade in active players. As in other high impact loading sports, the effect on area is specific involving mainly the pelvis and legs. The increment was totally unrelated to the calcium intake from dairy products. The fate of the increased BMC after intensive training is discontinued should be assessed. However, if the findings of the present cross-sectional study are supported by detailed longitudinal investigations, the presently reported observations might be important for the prevention of future osteoporotic fractures.

25OHD levels ≥20 ng/ml are needed for a better muscle function and strength. Assessing vitamin D nutritional status in adults aged ≥ 65 years would allow correcting hypovitaminosis D and improve muscle function and strength.

Objective: To evaluate the nutritional status of vitamin D in urban populations of healthy elderly people living at home, in different regions of Argentina. Design: Cross-sectional study. Subjects: In total, 386 ambulatory subjects over 65 y of age from seven cities (between latitude 261S and 551S) were asked to participate between the end of winter and the beginning of spring. Of these, 369 accepted, 30 were excluded because of medical history or abnormal biochemical determinations. Finally, 339 subjects (226 women and 113 men) (X7s.d.) (71.37 5.2 y) were included. Results: Serum 25OHD levels were lowest in the South (latitude range: 411S-551S): 14.275.6 ng/ml (Po0.0001vs North and Mid regions); highest in the North (261S-271S): 20.777.4 ng/ml (Po0.03 vs Mid, Po0.0001vs South); and intermediate in the Mid region (331S-341S) 17.978.2 ng/ml. Serum mid-molecule PTH (mmPTH) and 25OHD were inversely related: (r ¼ À0.24, Po0.001). A cutoff level of 25OHD at which serum mmPTH levels began to increase was established at 27 ng/ml. A high prevalence (87-52%) of subjects with 25OHD levels in the deficiency-insufficiency range (25OHD levels o20 ng/ml) was detected. Conclusion: This study shows that vitamin D deficiency/insufficiency in the elderly is a worldwide problem. Correction of this deficit would have a positive impact on bone health of elderly people. Sponsorship: Asociació n Argentina de Osteología y Metabolismo Mineral (AAOMM).

BackgroundGaucher disease (GD) presents with a range of signs and symptoms. Physicians can fail to recognise the early stages of GD owing to a lack of disease awareness, which can lead to significant diagnostic delays and sometimes irreversible but avoidable morbidities.AimThe Gaucher Earlier Diagnosis Consensus (GED‐C) initiative aimed to identify signs and co‐variables considered most indicative of early type 1 and type 3 GD, to help non‐specialists identify ‘at‐risk’ patients who may benefit from diagnostic testing.MethodsAn anonymous, three‐round Delphi consensus process was deployed among a global panel of 22 specialists in GD (median experience 17.5 years, collectively managing almost 3000 patients). The rounds entailed data gathering, then importance ranking and establishment of consensus, using 5‐point Likert scales and scoring thresholds defined a priori.ResultsFor type 1 disease, seven major signs (splenomegaly, thrombocytopenia, bone‐related manifestations, anaemia, hyperferritinaemia, hepatomegaly and gammopathy) and two major co‐variables (family history of GD and Ashkenazi‐Jewish ancestry) were identified. For type 3 disease, nine major signs (splenomegaly, oculomotor disturbances, thrombocytopenia, epilepsy, anaemia, hepatomegaly, bone pain, motor disturbances and kyphosis) and one major co‐variable (family history of GD) were identified. Lack of disease awareness, overlooking mild early signs and failure to consider GD as a diagnostic differential were considered major barriers to early diagnosis.ConclusionThe signs and co‐variables identified in the GED‐C initiative as potentially indicative of early GD will help to guide non‐specialists and raise their index of suspicion in identifying patients potentially suitable for diagnostic testing for GD.