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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

Hiv Medicine | July 15, 2015

Natsag J, Kendall MA, Sellmeyer DE, McComsey GA and Brown TT.

HIV Med. 2016 Mar;17(3):196-205




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 .


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).


ALN increased BMD more than placebo at both the lumbar spine (difference ALN  − placebo 2.64%;  = 0.011) and the total hip (difference 2.27%;  = 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;  < 0.0001] and total hip (difference 4.99%; 95% CI 2.40, 7.57;  = 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 ( = 0.014).


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.