Treatment of Human Immunodeficiency Virus Infection With Tenofovir Disoproxil Fumarate–Containing Antiretrovirals Maintains Low Bone Formation Rate, But Increases Osteoid Volume on Bone Histomorphometry

Abstract

Bone mineral density (BMD) loss is a known complication of human immunodeficiency virus (HIV) infection and its treatment, particularly with tenofovir disoproxil fumarate (TDF)‐containing antiretroviral regimens. Although renal proximal tubular dysfunction and phosphaturia is common with TDF, it is unknown whether BMD loss results from inadequate mineralization. We evaluated change in BMD by dual‐energy X‐ray absorptiometry (DXA) and bone histomorphometry by tetracycline double‐labeled transiliac crest biopsies in young men living with HIV before (n = 20) and 12 months after (n = 16) initiating TDF/lamivudine/efavirenz. We examined relationships between calciotropic hormones, urinary phosphate excretion, pro‐inflammatory and pro‐resorptive cytokines, and bone remodeling‐related proteins with changes in BMD and histomorphometry. Mean age was 29.6 ± 5.5 years, with mean CD4 + T cell count of 473 ± 196 cells/mm3. At baseline, decreased bone formation rate and increased mineralization lag time were identified in 16 (80%) and 12 (60%) patients, respectively. After 12 months, we detected a 2% to 3% decrease in lumbar spine and hip BMD by DXA. By histomorphometry, we observed no change in bone volume/total volume (BV/TV) and trabecular parameters, but rather, increases in cortical thickness, osteoid volume, and osteoblast and osteoclast surfaces. We did not observe significant worsening of renal phosphate excretion or mineralization parameters. Increases in PTH correlated with decreased BMD but not histomorphometric parameters. Overall, these data suggest abnormalities in bone formation and mineralization occur with HIV infection and are evident at early stages. With TDF‐containing antiretroviral therapy (ART), there is an increase in bone remodeling, reflected by increased osteoblast and osteoclast surfaces, but a persistence in mineralization defect, resulting in increased osteoid volume. © 2019 American Society for Bone and Mineral Research.

Osteoporosis and HIV Infection

“…Bone histomorphometry using tetracycline double-labeled transiliac crest biopsies has been reported in two studies: the first one in ART-naïve men and women in the 1990s, including 50% of patients with AIDS-defining opportunistic infections; and a recent one in ART-naïve men who underwent paired biopsies before and 12 months after initiation of TDF/lamivudine/efavirenz (Table 3 ) [ 38 , 39 ]. Overall, these data indicate low bone turnover with primarily abnormalities in bone formation and mineralization which are present in untreated PLWH with and without advanced HIV.…”

“…The pathophysiology of these tubulopathies remains unclear. In addition, the development of hypophosphatemia and osteomalacia is very rare and bone biopsy data reported earlier in the manuscript did not reveal worsening of mineralization with initiation of TDF [ 39 ]. The risk of developing tubulopathy seems to be lower with TAF [ 55 ].…”

A novel two-step, direct-to-PCR method for virus detection off swabs using human coronavirus 229E

“…Shaker-mill homogenization as a form of mechanical lysis has been proven time and again as a successful method for disrupting tissues, microorganisms, and biologic samples for downstream molecular analysis; however, these downstream applications often require the use of additional purification, isolation, or extraction procedures before those analyses can be completed [ 9 – 12 ]. While, shaker-mill homogenization procedures have not yet been applied directly to diagnostic technologies, its ability to lyse organisms and tissues far tougher than a virus have been well categorized [ 9 – 12 ]. Building off the increased need for novel viral diagnostic methodologies, which reduce the resources and time required for accurate viral pathogen detection, we felt it was time to examine the capabilities of shaker-mill homogenization for viral lysis to be used for downstream detection.…”

A Novel Two-Step, Direct-to-PCR Method for Virus Detection off Swabs using Human Coronavirus 229E

“…Shaker-mill homogenization as a form of mechanical lysis has been proven time and again as a successful method for disrupting tissues, microorganisms, and biologic samples for downstream molecular analysis; however, these downstream applications often require the use of additional puri cation, isolation, or extraction procedures before those analyses can be completed [9,10,11,12].…”

“…While, shaker-mill homogenization procedures have not yet been applied directly to diagnostic technologies, its ability to lyse organisms and tissues far tougher than a virus have been well categorized [9,10,11,12]. Building off the increased need for novel viral diagnostic methodologies, which reduce the resources and time required for accurate viral pathogen detection, we felt it was time to examine the capabilities of shaker-mill homogenization for viral lysis to be used for downstream detection.…”