Vitamin D , osteoprotegerin/receptor activator of nuclear factor‐kappa B 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‐kappa B 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 70 mg weekly or placebo for 48 weeks; all received calcium carbonate 500 mg/vitamin D 3 200  IU 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  < 32 ng/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.