In the Journals

Young MSM may not completely recover from PrEP-related bone density loss

Adolescents who take pre-exposure prophylaxis, or PrEP, for HIV prevention may experience a loss of bone mineral density during treatment. Most patients can experience partial or full recovery of BMD within 48 weeks after discontinuing the medication, but a recent study published in Clinical Infectious Diseases suggested that teens aged 15 to 19 years may not make a full recovery, especially in lumbar spine and whole body BMD Z-scores.

“PrEP use in adolescents and young adult [men who have sex with men (MSM)] raises concerns because bone growth continues into early adulthood,” Peter L. Havens, MD, MS, professor in the department of pediatrics at the Medical College of Wisconsin and the Children’s Hospital of Wisconsin, and colleagues wrote. “Peak bone mass, typically achieved in the mid-20s, predicts bone fractures later in life. Drugs decreasing bone mass or limiting bone growth during adolescence might increase fracture risk during adulthood.”

The researchers examined data from a preplanned extension phase of two open-label studies of PrEP with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF, Truvada) in young MSM aged 15 to 17 years and 18 to 22 years. The trials were identical and lasted 48 weeks. All participants who were included in the original trials who lost or failed to accrue bone or demonstrated signs of renal toxicity (n = 179) were included in the extension phase.

During the study, 12 participants discontinued treatment and 17 continued PrEP through other medical providers. The study was eventually narrowed down to 91 seronegative participants who had no further PrEP use following the trials and had one or more visit.

Havens and colleagues observed a decrease in lumbar spine BMD (LS-BMD), total hip BMD (HIP-BMD) and whole body BMD (WB-BMD) among these patients by week 24 of PrEP use, but LS-BMD and WB-BMD rebounded to baseline levels by week 48 and increased after discontinuing the medication. At 48 weeks following discontinuation of therapy, HIP-BMD and WB-BMD returned baseline levels, and LS-BMD exceeded the baseline.

Participants’ Z-scores for LS-BMD, HIP-BMD and WB-BMD were low on week 24 of treatment and remained low throughout their use of PrEP. After PrEP was stopped, Z scores for LS-BMD and WB-BMD remained below baseline, whereas HIP-BMD was returned to baseline.

According to the researchers, teens aged 15 to 19 years had more significant declines in Z-scores for LS-BMD and WB-BMD during PrEP use compared with those aged 20 to 22 years. The Z-scores improved among those aged 20 to 22 years but not among the younger participants. The researchers wrote that this “is a concerning finding.”

“While bone toxicity risk is counterbalanced by HIV acquisition protection, there is continued need for strategies to mitigate bone loss in at-risk young MSM during adolescence and early adulthood, when bone mass should be accruing,” Havens and colleagues wrote. – by Katherine Bortz

Disclosures: Havens reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

Adolescents who take pre-exposure prophylaxis, or PrEP, for HIV prevention may experience a loss of bone mineral density during treatment. Most patients can experience partial or full recovery of BMD within 48 weeks after discontinuing the medication, but a recent study published in Clinical Infectious Diseases suggested that teens aged 15 to 19 years may not make a full recovery, especially in lumbar spine and whole body BMD Z-scores.

“PrEP use in adolescents and young adult [men who have sex with men (MSM)] raises concerns because bone growth continues into early adulthood,” Peter L. Havens, MD, MS, professor in the department of pediatrics at the Medical College of Wisconsin and the Children’s Hospital of Wisconsin, and colleagues wrote. “Peak bone mass, typically achieved in the mid-20s, predicts bone fractures later in life. Drugs decreasing bone mass or limiting bone growth during adolescence might increase fracture risk during adulthood.”

The researchers examined data from a preplanned extension phase of two open-label studies of PrEP with emtricitabine and tenofovir disoproxil fumarate (FTC/TDF, Truvada) in young MSM aged 15 to 17 years and 18 to 22 years. The trials were identical and lasted 48 weeks. All participants who were included in the original trials who lost or failed to accrue bone or demonstrated signs of renal toxicity (n = 179) were included in the extension phase.

During the study, 12 participants discontinued treatment and 17 continued PrEP through other medical providers. The study was eventually narrowed down to 91 seronegative participants who had no further PrEP use following the trials and had one or more visit.

Havens and colleagues observed a decrease in lumbar spine BMD (LS-BMD), total hip BMD (HIP-BMD) and whole body BMD (WB-BMD) among these patients by week 24 of PrEP use, but LS-BMD and WB-BMD rebounded to baseline levels by week 48 and increased after discontinuing the medication. At 48 weeks following discontinuation of therapy, HIP-BMD and WB-BMD returned baseline levels, and LS-BMD exceeded the baseline.

Participants’ Z-scores for LS-BMD, HIP-BMD and WB-BMD were low on week 24 of treatment and remained low throughout their use of PrEP. After PrEP was stopped, Z scores for LS-BMD and WB-BMD remained below baseline, whereas HIP-BMD was returned to baseline.

According to the researchers, teens aged 15 to 19 years had more significant declines in Z-scores for LS-BMD and WB-BMD during PrEP use compared with those aged 20 to 22 years. The Z-scores improved among those aged 20 to 22 years but not among the younger participants. The researchers wrote that this “is a concerning finding.”

“While bone toxicity risk is counterbalanced by HIV acquisition protection, there is continued need for strategies to mitigate bone loss in at-risk young MSM during adolescence and early adulthood, when bone mass should be accruing,” Havens and colleagues wrote. – by Katherine Bortz

Disclosures: Havens reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.