BACKGROUNDRomosozumab, a monoclonal antibody that binds sclerostin, increases bone formation and decreases bone resorption. METHODSWe enrolled 7180 postmenopausal women who had a T score of -2.5 to -3.5 at the total hip or femoral neck. Patients were randomly assigned to receive subcutaneous injections of romosozumab (at a dose of 210 mg) or placebo monthly for 12 months; thereafter, patients in each group received denosumab for 12 months, at a dose of 60 mg, administered subcutaneously every 6 months. The coprimary end points were the cumulative incidences of new vertebral fractures at 12 months and 24 months. Secondary end points included clinical (a composite of nonvertebral and symptomatic vertebral) and nonvertebral fractures. RESULTSAt 12 months, new vertebral fractures had occurred in 16 of 3321 patients (0.5%) in the romosozumab group, as compared with 59 of 3322 (1.8%) in the placebo group (representing a 73% lower risk with romosozumab; P<0.001). Clinical fractures had occurred in 58 of 3589 patients (1.6%) in the romosozumab group, as compared with 90 of 3591 (2.5%) in the placebo group (a 36% lower risk with romosozumab; P = 0.008). Nonvertebral fractures had occurred in 56 of 3589 patients (1.6%) in the romosozumab group and in 75 of 3591 (2.1%) in the placebo group (P = 0.10). At 24 months, the rates of vertebral fractures were significantly lower in the romosozumab group than in the placebo group after each group made the transition to denosumab (0.6% [21 of 3325 patients] in the romosozumab group vs. 2.5% [84 of 3327] in the placebo group, a 75% lower risk with romosozumab; P<0.001). Adverse events, including instances of hyperostosis, cardiovascular events, osteoarthritis, and cancer, appeared to be balanced between the groups. One atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group. CONCLUSIONSIn postmenopausal women with osteoporosis, romosozumab was associated with a lower risk of vertebral fracture than placebo at 12 months and, after the transition to denosumab, at 24 months. The lower risk of clinical fracture that was seen with romosozumab was evident at 1 year. (Funded by Amgen and UCB Pharma; FRAME ClinicalTrials.gov number, NCT01575834.)

We present an analysis of the first 10 weeks of the severe acute respiratory syndrome (SARS) epidemic in Hong Kong. The epidemic to date has been characterized by two large clusters—initiated by two separate “super-spread” events (SSEs)—and by ongoing community transmission. By fitting a stochastic model to data on 1512 cases, including these clusters, we show that the etiological agent of SARS is moderately transmissible. Excluding SSEs, we estimate that 2.7 secondary infections were generated per case on average at the start of the epidemic, with a substantial contribution from hospital transmission. Transmission rates fell during the epidemic, primarily as a result of reductions in population contact rates and improved hospital infection control, but also because of more rapid hospital attendance by symptomatic individuals. As a result, the epidemic is now in decline, although continued vigilance is necessary for this to be maintained. Restrictions on longer range population movement are shown to be a potentially useful additional control measure in some contexts. We estimate that most currently infected persons are now hospitalized, which highlights the importance of control of nosocomial transmission.

Patients' age was strongly associated with outcome. The time between onset of symptoms and admission to hospital did not alter outcome, but shorter intervals will be important to the wider population by restricting the infectious period before patients are placed in quarantine.

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Several recent studies suggest that obesity may be a risk factor for fracture. The aim of this study was to investigate the association between body mass index (BMI) and future fracture risk at different skeletal sites. In prospective cohorts from more than 25 countries, baseline data on BMI were available in 398,610 women with an average age of 63 (range, 20-105) years and follow up of 2.2 million person-years during which 30,280 osteoporotic fractures (6457 hip fractures) occurred. Femoral neck BMD was measured in 108,267 of these women. Obesity (BMI 30 kg/m 2 ) was present in 22%. A majority of osteoporotic fractures (81%) and hip fractures (87%) arose in non-obese women. Compared to a BMI of 25 kg/m 2 , the hazard ratio (HR) for osteoporotic fracture at a BMI of 35 kg/m 2 was 0.87 (95% confidence interval [CI], 0.85-0.90). When adjusted for bone mineral density (BMD), however, the same comparison showed that the HR for osteoporotic fracture was increased (HR, 1.16; 95% CI, 1.09-1.23). Low BMI is a risk factor for hip and all osteoporotic fracture, but is a protective factor for lower leg fracture, whereas high BMI is a risk factor for upper arm (humerus and elbow) fracture. When adjusted for BMD, low BMI remained a risk factor for hip fracture but was protective for osteoporotic fracture, tibia and fibula fracture, distal forearm fracture, and upper arm fracture. When adjusted for BMD, high BMI remained a risk factor for upper arm fracture but was also a risk factor for all osteoporotic fractures. The association between BMI and fracture risk is complex, differs across skeletal sites, and is modified by the interaction between BMI and BMD. At a population level, high BMI remains a protective factor for most sites of fragility fracture. The contribution of increasing population rates of obesity to apparent decreases in fracture rates should be explored.

The beneficial effects of TC or RTE on musculoskeletal health are modest and may not translate into better clinical outcomes.

In 1998, a case-control study was conducted in Hong Kong on hospital patients with osteoarthritis of the hip (n = 138) and osteoarthritis of the knee (n = 658). Age- and sex-matched controls were recruited consecutively from general practice clinics in the same region. The following three risk factors were found to be associated with osteoarthritis of both the hip and the knee: first, a history of joint injury: for osteoarthritis of the hip, the odds ratio = 25.1 (95% confidence interval (CI): 3.5, 181) in men and 43.3 (95% CI: 11.7, 161) in women; for osteoarthritis of the knee, the odds ratio = 12.1 (95% CI: 3.4, 42.5) in men and 7.6 (95% CI: 3.8, 15.2) in women; second, climbing stairs frequently: for osteoarthritis of the hip, the odds ratio = 12.5 (95% CI: 1.5, 104.3) in men and 2.3 (95% CI: 0.6, 8.1) in women; for osteoarthritis of the knee, the odds ratio = 2.5 (95% CI: 1.0, 6.4) in men and 5.1 (95% CI: 2.5, 10.2) in women; third, lifting heavy weight frequently: for osteoarthritis of the hip, the odds ratio = 3.1 (95% CI: 0.7, 14.3) in men and 2.4 (95% CI: 1.1, 5.3) in women; for osteoarthritis of the knee, the odds ratio = 5.4 (95% CI: 2.4, 12.4) in men and 2.0 (95% CI: 1.2, 3.1) in women. In addition, subjects whose height and weight were in the highest quartile were at increased risk of osteoarthritis of the hip and knee, respectively (p < 0.05).

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