Vitamin D, osteoprotegerin/receptor activator of nuclear factor-kappaB ligand (OPG/RANKL) and inflammation with alendronate treatment in HIV-infected patients with reduced bone mineral density

Objectives: The aim of the study was to determine the effect of alendronate (ALN) on inflammatory markers and osteoprotegerin (OPG)/receptor activator of nuclear factor-kappaB ligand (RANKL), and to explore the associations of baseline systemic inflammation and vitamin D status on the bone mineral density (BMD) response to ALN. Methods: Eighty-two HIV-positive patients with lumbar spine T-score≤-1.5 were randomized to ALN 70mg weekly or placebo for 48 weeks; all received calcium carbonate 500mg/vitamin D3 200IU twice daily. Serum C-telopeptide (CTx) and BMD were assessed at baseline and week 48. Stored plasma samples in 70 subjects were assayed for levels of 25-hydroxyvitamin D (25(OH)D), OPG, RANKL, interleukin (IL)-6 and soluble receptors for tumour necrosis factor (TNF)-α 1 and 2 (sTNFR 1 and 2). Results: ALN increased BMD more than placebo at both the lumbar spine (difference ALN-placebo 2.64%; P=0.011) and the total hip (difference 2.27%; P=0.016). No within- or between-arm differences in OPG, RANKL or inflammatory markers were observed over 48 weeks. High baseline CTx and sTNFR2 were associated with a more robust BMD response to ALN over 48 weeks at the lumbar spine [difference 5.66%; 95% confidence interval (CI) 3.50, 7.82; P<0.0001] and total hip (difference 4.99%; 95% CI 2.40, 7.57; P=0.0002), respectively. Baseline 25(OH)D<32ng/mL was associated with larger increases in total hip BMD over 48 weeks, independent of ALN treatment (P=0.014). Conclusions: Among HIV-positive patients, higher baseline bone resorption and TNF-α activity were associated with an increased BMD response to ALN. The greater BMD response in those with lower vitamin D reinforces the importance of vitamin D supplementation with bisphosphonate treatment. 2015 British HIV Association.