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      Tenofovir-induced hypophosphatemic osteomalacia: how do bone mineral density, trabecular bone score and proximal hip geometry change with treatment?

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          Abstract

          Summary

          Tenofovir-induced osteomalacia secondary to proximal renal tubular dysfunction is not an uncommon complication known to occur. A 46-year-old woman was referred for the evaluation of osteoporosis which was diagnosed elsewhere. She had polyarthralgia, bony pains and proximal muscle weakness of 1 year duration. She was diagnosed to have HIV infection and was on antiretroviral therapy that consisted of tenofovir, lamivudine and efavirenz for the past 12 years. She had attained menopause 5 years back. On examination, she had bone tenderness, proximal myopathy and painful restriction of movement of her lower limbs. Investigations showed features of renal tubular acidosis, hypophosphatemia and raised alkaline phosphatase that were suggestive of osteomalacia. X-ray of the pelvis showed diffuse osteopenia and an MRI of the pelvis done showed multiple insufficiency fractures involving the head of femur on both sides. Following this, her tenofovir-based regimen was changed to abacavir, efavirenz and lamivudine with addition of neutral phosphate supplements and calcitriol. On follow-up after 6 months, she had significant improvement in her symptoms as well as in the bone mineral density at the lumbar spine (33.2%), femoral neck (27.6%), trabecular bone score (13.2%) and reduction in the buckling ratio at the narrow neck (6.3%), inter-trochanteric region (34%) and femoral shaft (28.8%). Tenofovir-induced osteomalacia is encountered in individuals on prolonged treatment with tenofovir. Treatment consists of changing to a non-tenofovir-based regimen, as well as supplementation of phosphate and calcitriol. Treatment results in remarkable improvement in symptoms and most densitometric indices.

          Learning points
          • Tenofovir is a nucleotide reverse transcriptase inhibitor (NRTI) and is a major drug in the treatment of retroviral and hepatitis B infections.

          • Tenofovir-related hypophosphatemic osteomalacia is related to proximal tubulopathy and is not an uncommon occurrence.

          • Treatment mandates changing to a non-tenofovir-based regimen with supplementation of neutral phosphate and calcitriol.

          • Treatment results in a significant improvement in bone mineral density, trabecular bone score and hip geometric parameters.

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          Most cited references11

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          Tenofovir-associated Fanconi syndrome: review of the FDA adverse event reporting system.

          S. Gupta (2008)
          Tenofovir disoproxil fumarate (TDF) is a commonly used HIV antiretroviral. A relatively uncommon adverse effect of this drug is Fanconi syndrome. What is known about this toxicity, especially in regards to concomitant medication use and outcomes, is limited to isolated case reports and small case series. Therefore, a retrospective review of the FDA Adverse Event Reporting System from 2001 through 2006 was conducted to examine demographics, concomitant medication use, outcomes, and temporal trends in reporting of Fanconi syndrome associated with TDF use. In this large case series of 164 subjects who met the case definition for Fanconi syndrome, the majority (83%) of the subjects received protease inhibitors (PI) with TDF; specifically, 74% of the total received a ritonavir-boosted PI. Didanosine was the most commonly (43%) prescribed nucleoside reverse transcriptase inhibitor (NRTI). The combination of didanosine with boosted PI was frequently observed (34%), and in particular, didanosine plus lopinavir/ritonavir was documented for 22%. Nearly half (46%) of the total were hospitalized. Fracture (2%) and requirement for dialysis (2%) were infrequent while Fanconi syndrome contributed to death in 2% of these subjects. Patients receiving ritonavir-boosted protease inhibitors or didanosine with tenofovir should be closely monitored for development of nephrotoxicity. Although reporting biases and the exclusion of reports with serious confounding conditions likely affected the estimation of outcomes in this case series, severe complications of tenofovir-associated Fanconi syndrome were uncommon.
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            Tenofovir and bone health.

            With continued improvements to the antiviral efficacy and tolerability of antiretroviral therapy, long-term safety of antiretroviral therapy 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.
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              A Review and Clinical Understanding of Tenofovir: Tenofovir Disoproxil Fumarate versus Tenofovir Alafenamide

              HIV is a serious chronic medical condition. Significant improvements in antiretroviral therapy have led to a transformation in its management. No curative treatment is available for HIV, and lifelong therapy is required with a combination of agents to control viral replication and prevent complications. Some of the older agents are notorious for many side effects, making patient compliance difficult, which is critical to preventing HIV resistance. Tenofovir is one of the newer, more tolerable, nucleotide reverse transcriptase inhibitors on the market; is a mainstay of many antiretroviral therapy combinations; and is now available in 2 different formulations, tenofovir disoproxil fumarate (TDF) and, the more recent, tenofovir alafenamide (TAF). These 2 formulations have very different pharmacokinetics, which seem to affect their efficacy and safety. This manuscript provides insight into the history of TDF and TAF development, their unique pharmacokinetics and pharmacology, clinically important adverse effects, monitoring, interactions, resistance, review of clinical studies, and guideline recommendations and clinical applications for tenofovir’s various indications.
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                Author and article information

                Journal
                Endocrinol Diabetes Metab Case Rep
                Endocrinol Diabetes Metab Case Rep
                EDM
                Endocrinology, Diabetes & Metabolism Case Reports
                Bioscientifica Ltd (Bristol )
                2052-0573
                11 January 2023
                2023
                : 2023
                : 22-0259
                Affiliations
                [1 ]Department of Endocrinology , Diabetes and Metabolism, Christian Medical College and Hospital, Vellore, India
                Author notes
                Correspondence should be addressed to K E Cherian; Email: kripaec@ 123456cmcvellore.ac.in
                Author information
                http://orcid.org/0000-0001-9249-3719
                http://orcid.org/0000-0003-3315-341X
                Article
                EDM220259
                10.1530/EDM-22-0259
                10083647
                36856368
                ed0389d1-7ac2-4e1a-814e-0a4502489980
                © the author(s)

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License..

                History
                : 21 March 2022
                : 11 January 2023
                Categories
                Adult
                Female
                Asian - Indian
                India
                Bone
                Bone
                Unusual Effects of Medical Treatment
                Unusual Effects of Medical Treatment

                adult,female,asian - indian,india,bone,unusual effects of medical treatment,march,2023

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