Evidence map›Paper›PMID 26177791›Full record

Trial reportHIV medicine2016

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.

J Natsag, M A Kendall, D E Sellmeyer, G A McComsey, T T Brown

Open access · greenAbstract readRandomized Controlled Trial
In one paragraph

Trial report in HIV medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 2 pooled it
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 2 syntheses or guidelines pooled it, 18 citations in OpenAlex.

  1. Adjunct Therapy for CD4Frontiers in immunology · 2021
    Pooled it
  2. Diagnosis, prevention, and treatment of bone fragility in people living with HIV: a position statement from the Swiss Association against Osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019
    Guideline
  3. Connecting the dots: (RANKLTranslational lung cancer research · 2025
    Article
  4. Review
  5. The effect ofFrontiers in immunology · 2023
    Review
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Bone health in HIV and hepatitis B or C infections.Therapeutic advances in musculoskeletal disease · 2017
    Review
  12. Review
  13. Vitamin D and bone loss in HIV.Current opinion in HIV and AIDS · 2016
    Review
  14. Impaired bone mineral accrual in prepubertal HIV-infected children: a cohort study.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious Diseases
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

J NatsagDivision of Endocrinology, Diabetes & Metabolism, Johns Hopkins University, Baltimore, MD, USA.
M A KendallCenter for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0001-9160-4544
D E SellmeyerMetabolic Bone Center, Johns Hopkins Bayview Medical Center, Baltimore, MD, USA.
G A McComseyDivision of Pediatric Infectious and Rheumatology Diseases, Case Western Reserve University, Cleveland, OH, USA.
T T BrownDivision of Endocrinology, Diabetes & Metabolism, Johns Hopkins University, Baltimore, MD, USA.
Johns Hopkins University · USCancer Research And Biostatistics · USCase Western Reserve University · US

Funding

Leadership and Operations Center (LOC), AIDS Clinical Trials Group (ACTG); LOC 1/UM1AI068636 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI Joseph J Eron, RAJESH T GANDHI · 2011 to 2026
$1073.1M
Statistical and Data Management Center (SDMC), AIDS Clinical Trials Group (ACTG)UM1AI068634 · NIAID · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · PI Marlene Ann Cooper, Michael David Hughes · 2011 to 2026
$246.6M
AIDS Clinical Trials Group NetworkU01AI068636 · NIAID · SOCIAL AND SCIENTIFIC SYSTEMS, INC. · PI KURITZKES, DANIEL R. · 2006 to 2010
$147.1M
STATISTICAL AND DATA MANAGEMENT CENTERU01AI038855 · NIAID · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI HUGHES, MICHAEL DAVID · 1996 to 2006
$78.1M
Statistical and Data Management Center for the AIDS Clinical Trials GroupU01AI068634 · NIAID · HARVARD SCHOOL OF PUBLIC HEALTH · PI HUGHES, MICHAEL DAVID · 2006 to 2010
$71.9M
Case Clinical Trials Unit: Administrative Supplement NOSI AI-20-031.UM1AI069501 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI George Yendewa · 2012 to 2026
$40.4M
The Johns Hopkins Baltimore-Washington-India Clinical Trials Unit (BWI CTU)UM1AI069465 · NIAID · JOHNS HOPKINS UNIVERSITY · PI Charles W. Flexner, Amita Gupta · 2012 to 2026
$34.1M
Case AIDS Clinical Trials UnitU01AI069501 · NIAID · CASE WESTERN RESERVE UNIVERSITY · PI LEDERMAN, MICHAEL MARCEL · 2007 to 2011
$14.7M
WOMEN'S HEALTH AGENDAU01AI027668 · NIAID · JOHNS HOPKINS UNIVERSITY · PI FLEXNER, CHARLES W. · 1988 to 2006
$8.7M
Johns Hopkins AIDS Clinical Trials UnitU01AI069465 · NIAID · JOHNS HOPKINS UNIVERSITY · PI FLEXNER, CHARLES W. · 2007 to 2011
$7.9M
Training for Clinician Scientists in Imaging ResearchT32EB006351 · NIBIB · JOHNS HOPKINS UNIVERSITY · PI POMPER, MARTIN G · 2006 to 2022
$4.0M
Mentoring in Endocrine and Metabolic Abnormalities in HIV and AgingK24AI120834 · NIAID · JOHNS HOPKINS UNIVERSITY · PI BROWN, TODD T · 2015 to 2025
$1.8M
NCCIH NIH HHS K23 AT002862NIAID NIH HHS AI069501NIAID NIH HHS K24 AI120834NIAID NIH HHS U01 AI027668NIAID NIH HHS U01 AI038855NIAID NIH HHS U01 AI068634NIAID NIH HHS U01 AI068636NIAID NIH HHS U01AI068636NIAID NIH HHS U01 AI069465NIAID NIH HHS U01 AI069501NIAID NIH HHS U01 AI38855NIAID NIH HHS UM1 AI068634NIAID NIH HHS UM1 AI068636NIAID NIH HHS UM1 AI069465NIAID NIH HHS UM1 AI069501NIAID NIH HHS UO1 AI068636NIAID NIH HHS UO1 AI38558NIBIB NIH HHS 5T32EB006351-07NIBIB NIH HHS T32 EB006351
6 · The paper itself

Abstract

objectivesThe 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.

methodsEighty-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).

resultsALN 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).

conclusionsAmong 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.

Indexed as

AdultAlendronateBone DensityBone Density Conservation AgentsBone ResorptionCholecalciferolDouble-Blind MethodDrug Therapy, CombinationFemaleHIV InfectionsHumansLumbar VertebraeMaleMiddle AgedRANK LigandTreatment OutcomeAlendronateBone Density Conservation AgentsCholecalciferolRANK LigandTNFSF11 protein, humanalendronatebone turnover markerinflammationlow bone mineral densityvitamin D

Identifiers

PMID26177791
PMCPMC4715784
OpenAlexW1601201234

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.