Tetsuo Nakano

CONTEXT: Weekly teriparatide injection at a dose of 56.5 μg has been shown to increase bone mineral density. OBJECTIVE: A phase 3 study was conducted to determine the efficacy of once-weekly teriparatide injection for reducing the incidence of vertebral fractures in patients with osteoporosis. DESIGN AND SETTING: In this randomized, multicenter, double-blind, placebo-controlled trial conducted in Japan, the incidence of morphological vertebral fractures by radiographs was assessed. PATIENTS: Subjects were 578 Japanese patients between the ages of 65 and 95 yr who had prevalent vertebral fracture. INTERVENTION: Subjects were randomly assigned to receive once-weekly s.c. injections of teriparatide (56.5 μg) or placebo for 72 wk. MAIN OUTCOME MEASURE: The primary endpoint was the incidence of new vertebral fracture. RESULTS: Once-weekly injections of teriparatide reduced the risk of new vertebral fracture with a cumulative incidence of 3.1% in the teriparatide group, compared with 14.5% in the placebo group (P < 0.01), and a relative risk of 0.20 (95% confidence interval, 0.09 to 0.45). At 72 wk, teriparatide administration increased bone mineral density by 6.4, 3.0, and 2.3% at the lumbar spine, the total hip, and the femoral neck, respectively, compared with the placebo (P < 0.01). Adverse events (AE) and the dropout rates by AE were more frequently experienced in the teriparatide group, but AE were generally mild and tolerable. CONCLUSION: Weekly s.c. administration of teriparatide at a dose of 56.5 μg may provide another option of anabolic treatments in patients with osteoporosis at higher fracture risk.

CONTEXT: Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral, nonvertebral, and hip fracture in predominantly Caucasian postmenopausal women with osteoporosis. OBJECTIVE: The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo. DESIGN AND SETTING: A randomized, double-blind, placebo-controlled trial with an open-label active comparator as a referential arm was conducted. PATIENTS: Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older, who had one to four prevalent vertebral fractures. INTERVENTION: Subjects were randomly assigned to receive denosumab 60 mg sc every 6 months (n = 500), placebo for denosumab (n = 511), or oral alendronate 35 mg weekly (n = 251). All subjects received daily supplements of calcium and vitamin D. MAIN OUTCOME MEASURE: The primary endpoint was the 24-month incidence of new or worsening vertebral fracture for denosumab vs placebo. RESULTS: Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7%, with incidences of 3.6% in denosumab and 10.3% in placebo at 24 months (hazard ratio 0.343; 95% confidence interval 0.194-0.606, P = .0001). No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study. CONCLUSION: These results provide evidence of the efficacy and safety of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis.

OBJECTIVES: To investigate the predictors of functional outcome and changes in the basic activities of daily living in older adults who sustained hip fractures, considering the level of ambulatory ability before injury. DESIGN: A prospective observational cohort study. SETTING: One university hospital and 13 community teaching hospitals. PATIENTS: A consecutive cohort of 650 patients who underwent surgery for a hip fracture between December 2004 and January 2006. MAIN OUTCOME MEASURES: Recovery of ambulatory ability and independence in activities of daily living 6 and 12 months after surgery. RESULTS: Ambulatory ability recovered to the prefracture level in approximately half of the patients 6 months after surgery, and those ratios changed little in the next 6 months. In patients who were community ambulators before fractures, the independence in bathing before fractures was a strong predictor of ambulatory ability after surgery, but this was not the case in the former household ambulator group. The attainment of assisted ambulation with a walking cane at hospital discharge was a reliable predictor of ambulatory ability in both former community ambulator and household ambulator groups. CONCLUSIONS: Ambulatory ability after hip fractures was considered to be determined within 6 months after surgery. There was some difference in prognostic factors for ambulatory ability according to the level of mobility before fractures. The attainment of single cane (T-cane) gait at hospital discharge can serve as a reliable predictor of ambulatory ability after fractures, irrespective of the level of mobility before the injury. LEVEL OF EVIDENCE: Prognostic Level I. See page 128 for a complete description of levels of evidence.