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.

TitleVitamin 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.
Publication TypeJournal Article
Year of Publication2016
AuthorsNatsag J, Kendall MA, Sellmeyer DE, McComsey GA, Brown TT
JournalHIV Med
Volume17
Issue3
Pagination196-205
Date Published2016 Mar
ISSN1468-1293
KeywordsAdult, Alendronate, Bone Density, Bone Density Conservation Agents, Bone Resorption, Cholecalciferol, Double-Blind Method, Drug Therapy, Combination, Female, HIV Infections, Humans, Lumbar Vertebrae, Male, Middle Aged, RANK Ligand, Treatment Outcome
Abstract

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 70 mg weekly or placebo for 48 weeks; all received calcium carbonate 500 mg/vitamin D3 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.

DOI10.1111/hiv.12291
Alternate JournalHIV Med.
PubMed ID26177791
PubMed Central IDPMC4715784
Grant ListUM1 AI069501 / AI / NIAID NIH HHS / United States
5T32EB006351-07 / EB / NIBIB NIH HHS / United States
U01 AI069465 / AI / NIAID NIH HHS / United States
AI069501 / AI / NIAID NIH HHS / United States
U01 AI38855 / AI / NIAID NIH HHS / United States
U01 AI038855 / AI / NIAID NIH HHS / United States
U01 AI027668 / AI / NIAID NIH HHS / United States
K24 AI120834 / AI / NIAID NIH HHS / United States
UO1 AI38558 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
U01 AI069501 / AI / NIAID NIH HHS / United States
UO1 AI068636 / AI / NIAID NIH HHS / United States
U01 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069465 / AI / NIAID NIH HHS / United States
T32 EB006351 / EB / NIBIB NIH HHS / United States
U01AI068636 / AI / NIAID NIH HHS / United States
K23 AT002862 / AT / NCCIH NIH HHS / United States
U01 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States