Fabio Vescini

Metabolic bone disease in HIV infection.

HIV mainly replicates in CD4þ T lymphocytes andmonocyte/macrophages causing severe immunologicalimpairment. In addition to the immune system, HIVinfection affects tissues and organs such as kidney, liver,the central nervous system, heart and bone showing acomplex pathogenesis [1].The advent and widespread use of highly activeantiretroviral therapy (HAART) in the last two decadeshasled toa markedimprovementinthe treatmentofHIVdisease even though viral infection cannot be eradicatedbecause HAART does not completely eliminate the viralreservoirs [2]. HAART has dramatically changed thecourseofHIVinfection froma fatalinfectiontoachronicand relatively manageable disease. The increased lifeexpectancyofHIVpatientsandtheeffectsofHAARThavechanged the management of HIV infection. Nowadaysmedical treatment is no longer focused solely on HIVinfection, opportunistic diseases and monitoring immunederangement, but also includes the control of metabolic,cardiovascular, liver, bone and kidney complications. Inparticular, bone alterations have been observed in thecourse of HIV disease representing a pivotal clinicalprobleminthemanagementofHIVpatientsespeciallyforapossible development of bone fractures [3]. The majorbonelesionsdetectableinHIVpatientsarerelatedtobonedemineralization (osteopenia/osteoporosis and osteoma-lacia) and osteonecrosis ([4] for a review).This report will discuss the pathogenesis, diagnosis andtreatment of major bone complications represented bybone demineralization diseases during HIV infection andHAART treatment.

Recommendations for Evaluation and Management of Bone Disease in HIV

Thirty-four human immunodeficiency virus (HIV) specialists from 16 countries contributed to this project, whose primary aim was to provide guidance on the screening, diagnosis, and monitoring of bone disease in HIV-infected patients. Four clinically important questions in bone disease management were identified, and recommendations, based on literature review and expert opinion, were agreed upon. Risk of fragility fracture should be assessed primarily using the Fracture Risk Assessment Tool (FRAX), without dual-energy X-ray absorptiometry (DXA), in all HIV-infected men aged 40-49 years and HIV-infected premenopausal women aged ≥40 years. DXA should be performed in men aged ≥50 years, postmenopausal women, patients with a history of fragility fracture, patients receiving chronic glucocorticoid treatment, and patients at high risk of falls. In resource-limited settings, FRAX without bone mineral density can be substituted for DXA. Guidelines for antiretroviral therapy should be followed; adjustment should avoid tenofovir disoproxil fumarate or boosted protease inhibitors in at-risk patients. Dietary and lifestyle management strategies for high-risk patients should be employed and antiosteoporosis treatment initiated.

Prevalence of Hypovitaminosis D and Factors Associated With Vitamin D Deficiency and Morbidity Among HIV-Infected Patients Enrolled in a Large Italian Cohort

Background: A high prevalence of hypovitaminosis D (hypD) in HIV-infected patients has been reported, but reasons are unclear. Methods: The 25 hydroxy vitamin D (vitD) concentration was measured in a sample of HIV-positive patients from Italy enrolled in the Icona Foundation Study. The change in absolute levels of vitD pre/post combination antiretroviral treatment was modelled by linear regression controlling for confounders and seasonality. Factors associated with hypD were identified using logistic regression analysis, and survival analysis was employed to evaluate the prognostic value of vitD concentration to predict severe diseases (diabetes, cardiovascular, renal), AIDS, and death. Results: We studied 810 patients contributing 1408 vitD measures. Median age was 36 years (range: 20-69). VitD insufficiency (30-75 nmol/L) and deficiency (<30 nmol/L) were found in 47% and 6% of the measures. Factors independently associated with vitD deficiency were African or Centre/South American nationality [odds ratio (OR): 4.16 vs. European, P = 0.04], the sample being collected in spring (OR: 11.27, P = 0.001) or in winter (OR: 4.22, P = 0.03) vs. summer, and a previous history of severe diseases (OR: 5.43, P = 0.03) or AIDS (OR: 2.44, P = 0.04). Over a median follow-up of 6.3 years, patients with vitD insufficiency were at higher risk of subsequent severe diseases than those with normal levels (relative hazard = 1.60, P = 0.05). Conclusions: Our analysis shows that despite the relatively young age of our HIV-infected population, the prevalence of hypD was high. Classic risk factors for hypD in the general population were confirmed in this setting. HypD seems to be moderately associated with the risk of severe disease, AIDS, and death.

Italian association of clinical endocrinologists (AME) position statement: drug therapy of osteoporosis

Treatment of osteoporosis is aimed to prevent fragility fractures and to stabilize or increase bone mineral density. Several drugs with different efficacy and safety profiles are available. The long-term therapeutic strategy should be planned, and the initial treatment should be selected according to the individual site-specific fracture risk and the need to give the maximal protection when the fracture risk is highest (i.e. in the late life). The present consensus focused on the strategies for the treatment of postmenopausal osteoporosis taking into consideration all the drugs available for this purpose. A short revision of the literature about treatment of secondary osteoporosis due both to androgen deprivation therapy for prostate cancer and to aromatase inhibitors for breast cancer was also performed. Also premenopausal females and males with osteoporosis are frequently seen in endocrine settings. Finally particular attention was paid to the tailoring of treatment as well as to its duration.

Bone Mass Loss in Patients With Human Immunodeficiency Virus Type 1 Infection: Association With Male Sex and Protease Inhibitor Therapy

The aim of our study was to evaluate the prevalence of osteopenia/osteoporosis in patients with human immunodeficiency virus (HIV) type 1 infection and to assess their possible correlation with antiretroviral therapy. Patients were enrolled among adult subjects with HIV type 1 infection referring to our tertiary care outpatient center. Bone mineral density was measured in the lumbar spine and femoral proximal head by dual-energy x-ray absorptiometry. A total of 95 HIV-infected patients (45 men) were enrolled: 12 subjects were naive to antiretroviral therapy, 18 received 3 nucleoside reverse-transcriptase inhibitors (NRTIs), 28 were treated with 2 NRTIs plus 1 non-NRTI, and 37 received 2 NRTIs plus 1 protease inhibitor (PI). Prevalence of osteopenia and osteoporosis according to lumbar T score was 37.9% and 9.5%, respectively, and osteoporosis was significantly more frequent in men than in women (20% vs. 0%; P < 0.001). The mean value of lumbar T score was significantly lower in PI-treated patients (−1.32 ± 0.48) than in naive subjects (−0.62 ± 0.24) or in those receiving 3 NRTIs (−0.68 ± 0.34) or 1 non-NRTI (−0.86 ± 0.44) (P < 0.05). Bone metabolism alterations associated with HIV infection probably have a multifactorial pathogenesis, but in our study, bone mass loss seems prompted by the male sex and a PI-based therapy.

The Effect of Thiazides on Bone Markers, Bone Mineral Density and Fractures

Abstract The literature data suggest a positive effect of thiazide diuretic treatment on bone health both by increasing bone mineral density and by decreasing the risk of fracture. The protective effect of thiazides seems to be linked both to the dosage and to the duration of treatment; moreover, the protective effects of thiazides in preserving bone mass and in decreasing the risk of fractures does not last long after discontinuation of treatment. Thiazides influence bone health by means of different mechanisms. In fact, they increase renal calcium reabsorption by inhibiting the sodium chloride cotransporter in the distal tubule, thus increasing sodium urinary excretion and decreasing urinary calcium excretion. Still, thiazides contribute to maintaining calcium homeostasis by increasing calcium intestinal absorption. Moreover, thiazides have a direct effect on bone cells, especially on osteoblast differentiation and bone mineral formation. Finally, it was suggested that thiazides prevent bone loss as they decrease the acid production by means of inhibition of carbonic anhydrase activity in the osteoclasts. The dual action shown by thiazides on both osteoblasts and osteoclasts could explain the reduced bone remodeling observed in patients taking these drugs, in the absence of changes in plasma parathyroid hormone levels. In conclusion, thiazides might play an interesting role in osteoporosis management, particularly in those patients affected by both hypertension and osteoporosis, but efficacy in reducing fractures and the safety of this treatment must still be evaluated by means of further randomized controlled clinical trials which have the reduction in fractures as primary outcomes.

Osteopatie metaboliche nelle malattie renali

Le alterazioni del metabolismo minerale e del tessuto osseo rappresentano una complicazione comune nella storia naturale di numerose nefropatie, e trovano la loro espressione piu tipica nei pazienti con insufficienza renale cronica in fase uremica (IRC). La comparsa di osteopatie metaboliche nei pazienti nefropatici e la conseguenza del ruolo chiave svolto dal rene nella regolazione dell’omeostasi minerale; infatti esso modula l’equilibrio esterno di calcio, fosforo e magnesio, controlla la sintesi di 1,25(OH)2D3, degrada e rimuove dal circolo l’ormone paratiroideo (PTH), contribuisce alla regolazione dell’equilibrio acido—base ed e il principale responsabile dell’escrezione di alluminio.

PI and OPG/RANKL levels in human osteoblast cells

Purpose of the study The association between loss of bone mineral density (BMD) and PI use is evidenced on several in vitro models and seems to have different etiology depending on specific molecule. Although an HAART regimen always contains one or more transcriptase inhibitors, there are no specific data available regarding specific PI action on BMD. However, some in vitro experiments showed that these compounds might induce the differentiation of osteoclast cells. In order to analyse the specific effect of each PI on human osteoblast we analysed OPG and RANKL levels after exposing the cells to each PI.