Bone, fracture and frailty

Hoy, Jennifer

doi:10.1097/coh.0b013e3283478741

Cited by 18 publications

(20 citation statements)

References 46 publications

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“…No toxic effects of vitamin D were observed. Even if life expectancy in HIV patients has markedly improved, frailty is still not a issue in most HIV-infected patients [44]. We therefore believe that the effect on muscle function may not lead to more falls.…”

Section: Discussionmentioning

confidence: 99%

Per oral substitution with 300000 IU vitamin D (Cholecalciferol) reduces bone turnover markers in HIV-infected patients

Piso

Rothen

et al. 2013

BMC Infect Dis

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BackgroundOsteoporosis and bone fractures seem to be higher in HIV-infected Patients compared to the general populations. Moreover, bone turnover markers are increased in patients on antiretroviral therapy and vitamin D deficiency is prevalent in HIV-infected patients. However, the influence of per oral cholecalciferol on bone metabolism in HIV infected patients is not well understood.MethodsWe measured the bone turnover markers in 96 HIV-infected patients: Bone specific alkaline phosphatase (BSAP), Pyridinoline (PYR), Desoxypyridinoline (DPD) and 25-OH vitamin D. If 25-OH vitamin D was below 75 nnol/L (87/96 patients), 300000 IU cholecalciferol was given per os. 25OH-vitamin D and bone turn over markers were determinded 3 month later. 25 OH-vitamin D was corrected for circannual rythm ][y'=y+17.875*sin0.12em)(2π365*italicday+2.06, whereas bone turnover markers were not corrected. The paired students t-Test was used to compare the two periods. No calcium supplementation or biphosphonate therapy was given.ResultsCorrected 25OH-vitamin D levels increased significantly after supplementation (42.7 ± 26.61 vs. 52.85 ± 21.8 nmol/L, p < 0.001). After supplementation, bone turnover markers were significantly lower. The values decreased for BSAP from 21.31 ± 14.32 to 17.53 ± 8.17 μg/L (p < 0.001), PYR from 74.57 ± 36.83 to 54.82 ± 21.43 nmol/mmol creatinine (p < 0.001) and DPD from 15.17 ± 8.34 to 12.61 ± 5.02 nmol/mmol creatinine (p = 0.01).ConclusionsAfter per oral substitution with cholecalciferol, bone formation as well as bone resorption markers decreased significant. We postulate a protective effect on bone structure with cholecalciferol supplementation.

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Section: Discussionmentioning

confidence: 99%

Per oral substitution with 300000 IU vitamin D (Cholecalciferol) reduces bone turnover markers in HIV-infected patients

Piso

Rothen

et al. 2013

BMC Infect Dis

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“…(2) HIV and ART have both been associated with bone loss and increased risk of fracture. (3)(4)(5)(6) Evidence is mixed but the general consensus is that ART exposure, particularly to tenofovir disoproxil fumarate (TDF), is associated with bone loss. (7,8) Even though the mechanism(s) is not entirely understood, it is hypothesized that the bone loss is related to TDF-induced renal phosphate wasting with subsequent skeletal demineralization.…”

Section: H Uman Immunodeficiency Virus (Hiv) Infection Is Associatedmentioning

confidence: 99%

“…HIV and ART have both been associated with bone loss and increased risk of fracture . Evidence is mixed but the general consensus is that ART exposure, particularly to tenofovir disoproxil fumarate (TDF), is associated with bone loss .…”

Section: Introductionmentioning

confidence: 99%

Changes in Bone Mineral Density, Body Composition, Vitamin D Status, and Mineral Metabolism in Urban HIV-Positive South African Women Over 12 Months

Hamill

Pettifor

Ward

et al. 2017

Journal of Bone and Mineral Research

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HIV infection and antiretroviral therapy (ART) are associated with bone loss and poor vitamin D status in Caucasian populations, though their relative roles are not known. No previous studies have examined longitudinal changes in areal bone mineral density (aBMD), measured by DXA, or in vitamin D status in HIV-positive African women. Of 247 premenopausal, urban, black African women from Soweto, South Africa, initially recruited, 187 underwent anthropometry, DXA scanning and blood and urine collections at both baseline and 12 months. Of these, 67 were HIVnegative throughout (Nref), 60 were HIV-positive with preserved CD 4 counts at baseline (Ppres) and 60 were HIV-positive with low CD 4 counts at baseline, eligible for ART by South African standards of care at the time (Plow). No participant had been exposed to ART at baseline. By 12 months, 51 Plow women had initiated ART, >85% of whom took combined tenofovir disoproxil fumarate (TDF), lamivudine and efavirenz. By 12 months, Plow and Nref, but not Ppres, increased in body weight and fat mass (group-by-timepoint p ≤0.001, p=0.002 respectively). Plow had significant decreases in aBMD of 2-3%, before and after size adjustment, at the femoral neck (p ≤0.002) and lumbar spine (p ≤0.001), despite significant weight gain. These decreases were associated with increased bone turnover but there were no significant differences or changes over time in vitamin D status, serum phosphate concentrations or renal phosphate handling. Excluding data from 9 Plow women unexposed to ART and 11 Ppres women who had initiated ART accentuated these findings, suggesting the bone loss in Plow was related to ART exposure. This is the first study describing DXA-defined bone loss in HIV-positive Sub-Saharan African women in Authors responsibilities: MMH, AP and JMP designed the study; MMH conducted the study; JMP and SAN provided senior oversight of the study in South Africa; KW provided senior oversight and interpretation of the DXA data; AP provided senior oversight and interpretation of the biochemical data; MMH and AP jointly conducted the statistical analysis and drafted the paper; all authors had full access to the data and contributed to interpretation of the findings. MMH and AP have responsibility for data integrity. All authors approved the manuscript for publication.The authors state that they have no conflicts of interest. Europe PMC Funders Group

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“…Bone loss in HIV‐infected adults is multifactorial. Greater bone loss has been reported with use of tenofovir disoproxil fumarate (TDF) and ritonavir‐boosted protease inhibitors (PIs) in the ART regimen . However, some bone loss occurs with all ART, probably because of increased bone catabolism after suppression of HIV viral load and immune reconstitution .…”

Section: Introductionmentioning

confidence: 99%

Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial

Hoy

Grund

Roediger

et al. 2017

Journal of Bone and Mineral Research

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Both HIV infection and antiretroviral therapy (ART) are associated with lower bone mineral density (BMD) and increased fracture risk. The relative contributions of ART and untreated HIV to BMD loss are unclear, it is important to quantify the effect of ART on bone. We compared the effect of early ART initiation (CD4 >500 cells/μL) with deferred ART on change in BMD in the START Bone Mineral Density substudy, a randomised trial evaluating the effect of immediate ART initiation versus deferring ART (to CD4 <350 cells/μL). BMD was measured annually at the lumbar spine and hip by dual-energy X-ray absorptiometry (DXA). Percent change in BMD by treatment assignment (intent-to-treat analysis) was estimated using longitudinal mixed models and linear regression. Baseline and follow-up DXA scans were available for 399 (195 immediate, 204 deferred) participants (median age 32 years, 80% non-white, 26% women, median CD4 count 642 cells/μL). ART (most commonly including tenofovir and efavirenz) was used for 95% and 18% of follow-up in the immediate and deferred ART groups, respectively. Through 2.2 years mean follow-up, immediate ART resulted in greater BMD declines than deferred ART at the hip (−2.5% vs. −1.0%; difference −1.5%, 95% CI −2.2 to −0.8, p<0.001) and spine (−1.9% vs. −0.4%; difference −1.6%, 95% CI −2.2 to −1.0, p<0.001). BMD declines were greatest in the first year of ART. In the immediate ART group, spine BMD stabilized after year 1, while hip BMD declined progressively over 2 years. After year 1, BMD changes were similar in the immediate and deferred groups. No clinical, HIV-related or ART characteristic predicted greater BMD loss in either group. All HIV treatment guidelines now recommend ART initiation at HIV diagnosis, due to the reduced risk of serious clinical outcomes. Better understanding of the longer term consequences of the observed reductions in BMD is needed.

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Bone, fracture and frailty

Abstract: This review examines the contributions from recent cohort studies to the understanding of the pathogenesis of bone loss in HIV, and the complex and poorly understood relationship between the effects of HIV and that of ART on bone loss.

Cited by 18 publications

References 46 publications

Per oral substitution with 300000 IU vitamin D (Cholecalciferol) reduces bone turnover markers in HIV-infected patients

Per oral substitution with 300000 IU vitamin D (Cholecalciferol) reduces bone turnover markers in HIV-infected patients

Changes in Bone Mineral Density, Body Composition, Vitamin D Status, and Mineral Metabolism in Urban HIV-Positive South African Women Over 12 Months

Immediate Initiation of Antiretroviral Therapy for HIV Infection Accelerates Bone Loss Relative to Deferring Therapy: Findings from the START Bone Mineral Density Substudy, a Randomized Trial

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