Objective The myopathy associated with anti-signal recognition particle (SRP) is a severe necrotizing immune-mediated disease characterized by rapidly progressive proximal muscle weakness, markedly elevated serum creatine kinase (CK) levels, and poor responsiveness to traditional immunosuppressive therapies. Reports on the efficacy of B cell depletion therapy for anti-SRP associated myopathy are mixed. We describe eight patients with anti-SRP associated myopathy and their response to treatment with the anti-CD20 monoclonal antibody rituximab. Methods We identified eight patients with myopathy who tested positive for anti-SRP antibodies by immunoprecipitation and were treated with rituximab as part of clinical care. We reviewed their medical records to assess clinical, serologic, and histologic characteristics and response to therapy. In five patients, serum was collected before and after rituximab therapy. Autoantibodies were detected by immunoprecipitation and quantitated by densitometry, and the percent decreases in anti-SRP autoantibody levels were calculated. Results Six of eight patients who had been refractory to standard immunosuppressive therapy demonstrated improved manual muscle strength and/or decline in CK levels as early as two months after rituximab treatment. Three patients sustained the response for twelve to eighteen months after initial dosing. All patients were continued on adjunctive corticosteroids, but dosages were substantially reduced after rituximab. Quantitative levels of serum anti-SRP antibodies also decreased after rituximab treatment. Conclusions B cell depletion therapy with rituximab is effective for patients with myopathy associated with anti-SRP. The substantial decrease in anti-SRP antibody levels after rituximab treatment also suggests that B cells and anti-SRP antibodies may play a role in the pathogenesis of this myopathy.

Objectives To systematically review and quantitatively synthesize the effect of vitamin D therapy on fall prevention in older adults. Design Systematic review and meta-analysis. Setting MEDLINE, CINAHL,Web of Science, EMBASE, Cochrane Library, LILACS, bibliographies of selected articles, and previous systematic reviews through February 2009 were searched for eligible studies. Participants Older adults (aged ≥60 years) who participated in randomized controlled trials that investigated the effectiveness of vitamin D therapy in the prevention of falls and used an explicit fall definition. Measurements Two authors independently extracted data including study characteristics, quality assessment, and outcomes. The I2 statistic was used to assess heterogeneity in a randomeffects model. Results Of 1,679 potentially relevant articles, 10 studies met inclusion criteria. In pooled analysis, vitamin D therapy (200-1000IU) reduced falls by 14% (relative risk [RR] 0.86;95% confidence interval 0.79-0.93;I2=7%) compared to calcium or placebo; number needed to treat=15. The following subgroups had significant fall reductions: community-dwelling (age<80 years), adjunctive calcium supplementation, no history of fractures/falls, duration>6 months, cholecalciferol, and dose≥800 IU. Meta-regression demonstrated no linear association of vitamin D dose or duration with treatment effect. Post-hoc analysis, including 7 additional studies (17 total) without explicit fall definitions, yielded smaller benefit (RR 0.92,0.87-0.98) and more heterogeneity (I2=36%) but found significant intergroup differences favoring adjunctive calcium versus none (p=0.001). Conclusion Vitamin D treatment effectively reduces the risk of falls in older adults. Future studies should investigate whether particular populations or treatment regimens may have greater benefit.

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Many drugs used for therapeutic interventions can cause unanticipated toxicity in muscle tissue, often leading to considerable morbidity. A drug-induced, or toxic, myopathy is defined as the acute or subacute manifestation of myopathic symptoms such as muscle weakness, myalgia, creatine kinase elevation, or myoglobinuria that can occur in patients without muscle disease when they are exposed to certain drugs. A brief review of agents with a known association with myotoxicity and the proposed mechanisms linked to that toxicity is outlined; however, the purpose of this review is to highlight recent discoveries and advances in the field of toxic myopathies that have practical implications for practicing physicians. Because many drug-related myopathies are potentially reversible at early stages, it is important for clinicians to recognize toxic myopathies early in their course to determine when to discontinue therapy and potentially prevent irreversible muscle damage.

At the approved dose of 200 mg once-daily combined with an XOI, LESU did not increase renal, cardiovascular or other adverse events compared with XOI alone, except for sCr elevations. With extended exposure in the core+extension studies, the safety profile was consistent with that observed in the core studies, and no new safety concerns were identified.

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