Effects of parathyroid hormone alone or in combination with antiresorptive therapy on bone mineral density and fracture risk - a meta-analysis

Aim The effects of parathyroid hormone (PTH) alone or in combination with antiresorptive therapy on changes in bone mineral density (BMD) and fracture risk were studied. Materials and methods Randomised placebo controlled trials were retrieved from the PubMed, Web of Science or Embase databases. Results PTH alone or in combination with antiresorptive drugs reduced vertebral [relative risk (RR)=0.36, 95% confidence interval (CI): 0.28-0.47, 2p < 0.01] and non-vertebral (RR=0.62, 95% CI: 0.48-0.82, 2p < 0.01) fracture risk and increased spine BMD by 6.6% (95% CI: 5.2-8.1%, 2p < 0.01) and hip BMD non-significantly by 1.0% (95% CI: -0.1 to 2.1%, 2p=0.08) during 11-36 months of follow-up (13 trials). The gain in spine and hip BMD tended to increase with the length of the PTH treatment. No significant effect of study duration on fracture risk could be demonstrated. The major adverse events were hypercalcaemia, nausea and discomfort at the injection sites. Only limited data are currently available on fracture risk reduction with PTH plus antiresorptive therapies. Conclusion Although the number of studies on non-vertebral fractures is limited, our pooled analysis revealed that PTH alone or in combination with antiresorptive drugs would appear to be able to reduce the risk of vertebral and non-vertebral fractures and to increase spine and perhaps hip BMD. However, these analyses were based on cross-sectional data - i.e. based on indirect comparisons - and further studies with a direct comparison of study duration are necessary. No studies comparing PTH, PTH plus antiresorptive drugs and antiresorptive drug versus placebo in a factorial design are available; consequently, we were unable to draw any conclusions on the superiority of PTH plus antiresorptive drug versus antiresorptive drug or PTH alone with respect to BMD or fractures.