Abstract Disclosure: C.E. Guillen Lopez: None. L.A. Sanchez Ato: None. A. Patel: None. A. Molkina: None. T. Ayub: None. L. Robles: None. A. Arce Gastelum: None. Osteoporosis presents a substantial public health challenge, contributing significantly to morbidity and mortality through fractures. While postmenopausal osteoporosis is common, secondary osteoporosis affects a significant number of patients, including over 30% of postmenopausal and 50-80% of men. People living with HIV (PLWH) experience age-related medical comorbidities earlier and more extensively than those without HIV. The compromised bone health in PLWH is attributed to factors associated with the virus, antiretroviral therapy (ART) side effects, and health disparities such as inadequate nutrition, low body weight, hypogonadism, vitamin D deficiency, and increased recreational substance use. More recently, it has become apparent that vertebral fractures are more common in PLWH, with a prevalence of 11.1% and a 2.30-fold more significant risk than the general population. Low bone mass density (BMD) is twice as common in PLWH, increasing to 3 times as common in PLWH on ART. ART initiation leads to transient bone loss with nucleotide reverse transcriptase inhibitors such as tenofovir disoproxil fumarate (TDF) and protease inhibitors, causing higher BMD loss. In contrast, integrase and specific reverse-transcriptase inhibitors have minimal adverse effects on BMD. The newer formulation, tenofovir alafenamide (TAF), is believed to have a more favorable impact on bone health than TDF. The repercussions of diminished bone health, particularly osteoporotic fractures, have significant medical and economic implications. They are leading to early mortality, disability, and a loss of independence. The HIV Medicine Association (HIVMA) and Infectious Diseases Society of America (IDSA) recommend BMD screening for all HIV-infected patients at 50 years. 58-year-old male PLWH reveals a history of osteoporosis with multiple spinal (L1, L4-5, S1) and bilateral wrist fractures on TDF for 15 years. The patient has been treated with bisphosphonates. Alendronate was initially prescribed, but due to acid reflux side effects, zoledronic acid was a better option. Despite various ART regimens, Dolutegravir/Lamivudine was started four years ago without further fractures. Recent bone density assessments showed improvement in the lumbar spine, returning to a normal range with a T-score of 0.6. However, the left femoral neck remains at -2.5, and the right femoral neck is at -2.2, showing minimal change. To enhance BMD in PLWH on ART, transitioning to alternatives with lower bone loss associations and using bisphosphonates as tolerated are suggested. As the HIV-infected population ages, proactive screening for low BMD is vital to manage evolving health needs and prevent bone-related complications. A holistic approach includes evaluation for secondary etiologies of osteoporosis, medical treatment, and vitamin D and calcium supplementation. Presentation: 6/3/2024