Pre-exposure prophylaxis (PrEP), using tenofovir disoproxil fumarate (TDF), can effectively prevent HIV acquisition. However, TDF can cause changes in bone mineral density (BMD). There is little information on the use of PrEP among patients with bone disease. We present a case report of a female with pre-existing osteoporosis who was prescribed PrEP. Over the course of 9 months of consistent PrEP use, verified by dried blood spot testing, we report a lack of BMD changes on serial dual-emission X-ray absorptiometry scans in this patient. This case can inform PrEP care for patients with pre-existing bone disease.