Proteinuria Is Associated With Increased Risk of Fragility Fracture in Men With or at Risk of HIV Infection.

BACKGROUND: Proteinuria has been associated with bone loss and fractures in general population, but data in HIV-infected population are lacking. SETTING: Prospective, multicenter cohort study of men with or at risk of HIV infection. METHODS: Between 2006 and 2015, urine protein measurements and bone fracture histories were ascertained semiannually in 947 HIV-infected (HIV+) and 969 HIV-uninfected (HIV-) men aged 40 years or older. Proteinuria was defined as protein-to-creatinine ratio ≥200 mg/g at ≥2 consecutive visits. Outcome measures (1) all fractures (excluding fractures of skull, face, and digits) and (2) fragility fractures (fractures of vertebral column, femur, wrist, and humerus). Multivariable Cox proportional hazards models assessed the association between proteinuria and fracture after adjusting for additional risk factors. RESULTS: The overall period prevalence of proteinuria was higher among HIV+ than HIV- (29% vs 6%, P < 0.001). Men with proteinuria had a significantly higher risk of fragility fracture compared with men without proteinuria [adjusted hazard ratio (aHR) = 2.29 (1.12-4.66)] and did not differ by HIV serostatus (p-interaction = 0.83). The risk of all fractures was not statistically different between men with or without proteinuria [aHR = 1.31 (0.84-2.05)]. Among HIV+ men, the association between confirmed proteinuria and fragility fracture was attenuated [aHR = 2.12 (0.95-4.73)] after additional adjustment for CD4 T-cell count/mm, history of AIDS, the presence of detectable plasma HIV-1 RNA, and cumulative exposure to tenofovir disoproxil fumarate. CONCLUSIONS: Proteinuria was more common in HIV+ than in HIV- men and was a strong independent risk factor for fragility fracture regardless of HIV serostatus. Proteinuria should prompt consideration of a thorough evaluation for bone disease among HIV+ persons.

An increased rate of fracture occurs a decade earlier in HIV+ compared with HIV- men.

OBJECTIVES: To determine the incidence of fracture among aging HIV-infected (HIV+) and uninfected men (HIV-). To evaluate factors independently associated with fracture risk. DESIGN: Prospective, multicenter cohort study of men with or at risk for HIV. METHODS: Outcome measures: all fractures (excluding skull, face and digits) and fragility fractures (vertebral column, femur, wrist and humerus) were collected semiannually in 1221 HIV+ and 1408 HIV- men aged at least 40. Adjusted incident rate ratios (aIRR) with an interaction term for age (40-49, 50-59 and ≥60 years) and HIV serostatus were estimated with Poisson regression models accounting for additional risk factors. RESULTS: Fracture incidence increased with age among both HIV+ and HIV- men. Although there was no significant difference in fracture incidence by HIV serostatus among men aged 40-49 years, the HIV+ men aged 50-59 years had a significantly higher incidence of all fractures [aIRR: 2.06 (1.49, 2.84)] and fragility fractures [aIRR: 2.06 (1.21, 3.50)] compared with HIV- participants of similar age. HIV modified the effect of age on all fractures (P = 0.002) but did not significantly modify the effect for fragility fractures (P = 0.135). Hypertension increased the rate of all fractures by 32% after adjustment for covariates [aIRR: 1.32 (1.04, 1.69)]. CONCLUSION: Fracture incidence increased with age among HIV+ and HIV- men but was higher among HIV+ men. A significant increase in fracture incidence was found among 50-59-year-old HIV+ men, highlighting the importance of osteoporosis screening for HIV-infected men above the age of 50.

The effect of dietary protein source on serum lipids: Secondary data analysis from a randomized clinical trial.

BACKGROUND: Plant-based diets can lower serum lipids. Whether soy foods offer additional benefits remains controversial. OBJECTIVE: To determine the effect of different protein sources on serum lipids and glucose metabolism, emphasizing comparisons between soy and nonsoy plant-based diets. METHODS: Secondary data analysis. A total of 173 postmenopausal women were randomized to 1 of 4 weighed metabolic diets for 6 weeks. Diets were equivalent in energy, protein, and fat with at least 80% of protein from either nondairy animal, dairy, nonsoy plant, or soy foods. At baseline and week 6, total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, glucose, and insulin were measured. Changes in variables during the diet period were compared within and among groups using t tests and analysis of variance. RESULTS: TC decreased 38.8 mg/dL in soy group (P < .001 vs dairy and animal) and 30.5 mg/dL in nonsoy plant group (P = .003 vs dairy, .03 vs animal). LDL decreased 28.3 mg/dL in soy group (P < .001 vs dairy and animal) and 20.6 mg/dL in nonsoy plant group (P = .005 vs dairy, .06 vs animal). HDL decreased 12 mg/dL in soy group (P = .003 vs dairy, .0008 vs animal) and 10 mg/dL in nonsoy plant group (P = .05 vs dairy, .04 vs animal). There were no significant differences in lipid changes between soy and nonsoy plant-based diets. No differences among groups in changes in triglycerides, glucose, or insulin were seen. CONCLUSIONS: Soy and nonsoy plant-based diets reduced TC and LDL with no significant difference between them. Further studies are needed to determine the specific lipid-lowering components of both soy and nonsoy plant foods.

Fibroblast Growth Factor 23-Mediated Bone Disease.

Fibroblast growth factor 23 (FGF23) is an important regulator of phosphate and vitamin D metabolism and its excessive or insufficient production leads to a wide variety of skeletal disorders. This article reviews the FGF23-α-Klotho signaling pathway, highlighting the latest developments in FGF23 regulation and action, and describes the disorders associated with FGF23 excess or deficiency.

The dynamic skeleton.

Adding to its well-known roles in locomotion and calcium balance, the skeleton has recently been appreciated as a true endocrine organ. Bone remodeling, a highly dynamic process, requires synchronized activities and crosstalk between bone cells. Discovery and characterization of the Wnt/ß catenin pathway in bone formation, FGF23 regulation of phosphate homeostasis and osteocalcin in energy and glucose homeostasis have reframed our view of the skeleton from simply a target tissue of the endocrine system to an endocrine tissue itself. This comprehensive review provides an overview of these complex pathways, their application to human bone disorders and implications for developing diagnostic and therapeutic targets.