Downregulation of Gnas, Got2 and Snord32a following tenofovir exposure of primary osteoclasts

Grigsby, Iwen F.; Pham, Lan; Gopal, Raj K.; Mansky, Louis M.; Mansky, Kim C.

doi:10.1016/j.bbrc.2009.12.039

Cited by 36 publications

(27 citation statements)

References 30 publications

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“…In vitro studies have demonstrated altered expression of genes involved in cell signaling, energy and amino acid metabolism in osteoclasts and osteoblasts exposed to physiological doses of TFV (5, 6). TFV exposure resulted in abnormal calcium deposition in a study utilizing a sarcoma cell line (7).…”

Section: Potential Mechanisms Of Tenofovir Toxicity In Bonementioning

confidence: 99%

Tenofovir and bone health

Grant

Cotter

2016

Current Opinion in HIV and AIDS

128

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Purpose of review With continued improvements to the antiviral efficacy and tolerability of antiretroviral therapy (ART), long term safety of ART has become paramount. Low bone mineral density and fragility fractures are more common in HIV-infected individuals than in the general population. The aims of this review are to describe potential mechanisms underlying the adverse effects of tenofovir on bone, clinical studies of tenofovir disoproxil fumarate (TDF) and bone, and more recent bone data on tenofovir alafenamide (TAF). Recent finding Several studies have demonstrated an approximately 1–3% greater bone mineral density loss with TDF compared with other agents. Recent studies with TAF have shown improved bone (and renal) safety with similar virologic efficacy when compared to TDF. Summary Given these findings, TDF-containing regimens may be gradually replaced with non-TDF containing regimens for the treatment of HIV infection, especially in those at higher risk for fragility fracture.

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Section: Potential Mechanisms Of Tenofovir Toxicity In Bonementioning

confidence: 99%

Tenofovir and bone health

Grant

Cotter

2016

Current Opinion in HIV and AIDS

128

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“…TDF appears to have effects on both bone and hormones [such as fibroblast growth factor-23 and 1,25(OH)2D] that may indirectly increase PTH. 45–47 TDF use can also result in renal tubular dysfunction stimulating production of PTH and in renal phosphate-wasting 44 which may, in part, be PTH-mediated. 12 In HIV-infected adolescents, baseline PTH levels were higher in TDF users regardless of 25(OH)D status.…”

Section: Discussionmentioning

confidence: 99%

Associations of Low Vitamin D and Elevated Parathyroid Hormone Concentrations With Bone Mineral Density in Perinatally HIV-Infected Children

Jacobson

Stephensen

Miller

et al. 2017

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Perinatally HIV-infected (PHIV) children have, on average, lower bone mineral density (BMD) than perinatally HIV-exposed uninfected (PHEU) and healthy children. Low 25-hydroxy vitamin D [25(OH)D] and elevated parathyroid hormone (PTH) concentrations may lead to suboptimal bone accrual. Methods PHIV and PHEU children in the Pediatric HIV/AIDS Cohort Study had total body (TB) and lumbar spine (LS) BMD and bone mineral content (BMC) measured by dual-energy x-ray absorptiometry; BMD z-scores (BMDz) were calculated for age-sex. Low 25(OH)D was defined as ≤20 ng/mL and high PTH as >65 pg/mL. We fit linear regression models to estimate average adjusted differences in BMD/BMC by 25(OH)D and PTH status, and log-binomial models to determine adjusted prevalence ratios (aPR) of low 25(OH)D and high PTH in PHIV relative to PHEU children. Results PHIV children (N=412) were older (13.0 vs.10.8 yr) and more often black (76% vs. 64%) than PHEU (N=207). Among PHIV, children with low 25(OH)D had lower TB-BMDz (−0.38 SD; 95%CI: −0.60 to −0.16) and TB-BMC (−59.1 g; 95%CI: −108.3 to −9.8); high PTH accompanied by low 25(OH)D was associated with lower TB-BMDz. Among PHEU, children with low 25(OH)D had lower TB-BMDz (−0.34 SD; 95%CI: −0.64 to −0.03). Prevalence of low 25(OH)D was similar by HIV status (aPR1.00; 95%CI: 0.81 to 1.24). High PTH was 3.17 (95%CI: 1.25 to 8.06) times more likely in PHIV children. Conclusion PHIV and PHEU children with low 25(OH)D may have lower BMD. Vitamin D supplementation trials during critical periods of bone accrual are needed.

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“…Negative influence on the bone tissue was well documented for the HIV protease inhibitors and tenofovir, a nucleotide reverse transcriptase inhibitor, currently used in a half of cART treated patients in Poland [18][19][20]. In HIV infection the higher bone tissue turnover, involving its synthesis and resorption, was described.…”

Section: Osteoporosis and The Hiv Infectionmentioning

confidence: 98%

Osteoporosis and vitamin D deficiency in HIV-infected patients: Genetic and classical factors compared to the HIV-associated ones – Review

Bander

Parczewski

2012

HIV & AIDS Review

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a b s t r a c tOsteopenia and osteoporosis are often found among people living with human immunodeficiency virus infection (HIV). Irrespective of age, osteopenia is found in 60% of such patients, while osteoporosis in 10-15%. Reasons for the decreased bone mineral density in this infection are diverse: possibility of osteoblast and osteoclast infection by HIV, chronic immune activation, vitamin D3 deficiency, secondary hyperparathyroidism or adverse effects of the antiretroviral treatment, and a range of others.Important factor in an osteoporosis development is related to the genetic variability. For more than 10 years genetic variants associated with bone mineralization, osteopenia and osteoporosis, mainly single nucleotide polymorphisms, have remained in the research spotlight. The most important ones identified to date include regions coding for the vitamin D3 receptor, estrogen receptors, parathyroid hormone, osteoprotegerin, type I A1 collagen and RANK/RANKL system.Vitamin D deficiency is of the primary importance not only for the adequate calcium-phosphate metabolism, but also for the regulation of the immunologic processes, cancer protection or pathogenesis of diabetes and hypertension. The most recent studies on the European and American populations confirm notable decrease of the vitamin D levels also among HIV infected patients.

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Downregulation of Gnas, Got2 and Snord32a following tenofovir exposure of primary osteoclasts

Cited by 36 publications

References 30 publications

Tenofovir and bone health

Tenofovir and bone health

Associations of Low Vitamin D and Elevated Parathyroid Hormone Concentrations With Bone Mineral Density in Perinatally HIV-Infected Children

Osteoporosis and vitamin D deficiency in HIV-infected patients: Genetic and classical factors compared to the HIV-associated ones – Review

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