Table 2.

Determinants of osteoporosis and fracture in people living with HIV over the time-course of HIV infection

	Before HIV infection	Untreated HIV infection	ART initiation	Long-term ART-stable PLWH
Classical risk factors of osteoporosis and fracture - Non-modifiable: Age, Caucasian ethnicity, prior fractures, parent history of hip fracture - Modifiable: Low BMI, lifestyle: tobacco, alcohol, low physical activity, poor nutrition: low calcium and protein intakes, vitamin D deficiency, hypogonadism in men and early menopause, comorbidities and drugs (glucocorticoids), fall risk	++	++	++	++
Immune and bone cell HIV infection - Increased osteoclasts differentiation and activity - Decrease osteoblast activity - Pro-adipogenic and inflammatory environment - Immune system modulation	0	++	+++	0
Direct effect of ART - Renal tubulopathy and urine phosphate wasting (tenofovir) - Interaction with vitamin D metabolism	0	+	+	+
Gut microbial dysbiosis - HIV-induced gut dysbiosis promoting pro-inflammatory environment - ART effects on gut microbiota	0/+	+++	++	+
BMD changes	↔ \↘	↘↘	↘↘↘	↔ \↘

The respective contribution of each determinant block at the population level is indicated (0, no contribution, + low, + + medium, +++ high), and may vary at patient individual levels. Some classical risk factors may be corrected (diet improvement, stop tobacco or alcohol, increase physical activity) while others appears (aging, hypogonadism, comorbidities) in long-term ART-stable PLWH

HIV human immunodeficiency virus, ART antiretroviral therapy; PLWH people living with HIV, BMD bone mineral density