Effects of alendronate for treatment of glucocorticoid-induced osteoporosis: A meta-analysis of randomized controlled trials.

BACKGROUND: Alendronate has been used to prevent or treat glucocorticoid-induced osteoporosis (GIO), data regarding its efficacy are inconsistent. We conducted the current systematic review and meta-analysis to evaluate both efficacy and safety of alendronate in the treatment of GIO. METHODS: PubMed, Embase, the Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing Databases were searched up through March 1, 2018. Randomized controlled trials (RCTs) involving patients which received alendronate treatment were included. Outcome measures were bone mineral density (BMD) changes, bone fractures, and adverse reactions. Data from the individual studies were pooled using random or fixed effect models based on heterogeneity. Effect size was reported as standardized mean differences (SMD) for continuous outcomes and pooled odds ratios (OR) for dichotomous outcomes, with 95% confidence interval (CI). RESULTS: Overall, 10 studies involving 1002 patients were included in the present investigation. Alendronate treatment significantly increased BMD of the lumbar spine and femoral neck during 6 to 24 months. These beneficial effects were apparent at 12 months after treatment for the lumbar spine but not the femoral neck BMD. Alendronate treatment did not significantly change fracture risk nor induce significant differences in adverse gastrointestinal effects. CONCLUSION: Alendronate significantly increases BMD of the lumbar spine and femoral neck in patients with GIO, but does not appear to reduce the risk of fractures. As relatively insufficient data regarding the GIO fracture incidence has been reported, more RCTs need to be carried out to determine the efficacy of alendronate in the prevention of GIO fracture.

Effects of teriparatide versus alendronate for treatment of postmenopausal osteoporosis: A meta-analysis of randomized controlled trials.

OBJECTIVES: Osteoporosis remains a clinical challenge. Teriparatide is an anabolic drug and alendronate is an antiresorptive agent; both are used in the treatment of osteoporosis. Comprehensive reviews investigating the comparative safety and efficacy of teriparatide versus alendronate are scarce. Therefore, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the safety and efficacy of teriparatide versus alendronate for the treatment of postmenopausal osteoporosis. METHODS: We conducted a comprehensive literature review of the PubMed, EMBASE, Cochrane Controlled Trials Registry, and the China Academic Journal Network Publishing databases for relevant RCTs of teriparatide versus alendronate in postmenopausal osteoporosis patients. Outcome measures were percentage change in lumbar spine and femoral neck bone mineral density (BMD) and incidence of vertebral and nonvertebral fractures. Effect size was reported as weighted mean differences (WMDs) for continuous outcomes and odds ratios (OR) for dichotomous outcomes, with associated 95% confidence intervals (CIs). RESULTS: Six trials involving 618 patients were included. The meta-analysis demonstrated a significant increase in lumbar spine BMD (WMD: 3.46, 95% CI: 2.15-4.77, P < .00001), but not femoral neck BMD (WMD = 1.50, 95% CI: 0.04-2.95, P = .04), in postmenopausal osteoporosis patients treated with teriparatide compared with alendronate for 6 to 18 months. These beneficial effects were apparent in the lumbar spine at 12 months of treatment (WMD: 4.49, 95% CI: 2.57-6.40, P < .01). Teriparatide was not superior to alendronate in reducing fracture risk (OR: -0.03, 95% CI: -0.12 to 0.07; P = .52). CONCLUSION: Teriparatide may be superior to alendronate for increasing lumbar spine BMD in postmenopausal osteoporosis. The efficacy and safety of long-term teriparatide and alendronate treatment in postmenopausal osteoporosis should be further investigated in clinical trials.

Functions and mechanisms of intermittent negative pressure for osteogenesis in human bone marrow mesenchymal stem cells.

The present study aimed to determine the mechanism by which low­intensity intermittent negative pressure affects the differentiation and proliferation of human mesenchymal stem cells (MSCs). Alkaline phosphatase (ALP) activity, type I collagen and vascular endothelial growth factor (VEGF) were detected to analyze differentiation. MTT and flow cytometry were employed to measure proliferation and apoptosis. Western blot analysis was used to examine endoplasmic reticulum (ER) stress­associated factors. This study was divided into two groups, including a normal group (without any treatment) and vacuum group (treated with a vacuum). There was a significant decrease in the proliferation of cells in the vacuum group. The number of cells in S phase was reduced significantly, while the rate of apoptosis and the activity of ALP were markedly increased under vacuum conditions. Expression of collagen type I and VEGF was significantly increased, and the ratio of osteoprotegrin to osteoprotegrin ligand was decreased significantly in the vacuum group. ER stress­associated proteins, p­PRKR­like ER kinase, inositol­requiring enzyme 1 and cleaved activating transcription factor 6, as well as the downstream factors, were activated when treated with negative pressure. In conclusion, treatment with low­intensity and intermittent negative pressure may inhibit the proliferation of MSCs and trigger ER stress­associated cellular apoptosis, further enhancing osteogenesis activity and inducing differentiation to osteoblasts.