Hormone replacement therapy (HRT) can reduce bone loss in postmenopausal women, but there is limited research on long-term outcomes in real-world populations. In the largest study to date, researchers examined the impact of HRT on bone health in more than 137,000 postmenopausal women over five years. They concluded that women who initiate early HRT after a menopause diagnosis face a significantly lower risk of osteoporosis over the long term.

Presented at the 2026 Annual Meeting of the American Academy of Orthopaedic Surgeons (AAOS), the study, “Early Hormone Replacement Therapy and Long-Term Bone Health in Postmenopausal Women: A Real-World Propensity-Matched Study,” also indicated that early HRT reduces fracture risk in postmenopausal women by 13%. The data adds to a growing body of research suggesting that early hormone replacement therapy can improve bone density during the postmenopausal period.

“As our population ages, age-related conditions like bone loss have become common, and the risk of falling and fracturing bones increases exponentially. From an orthopedic standpoint, this often leads to hospitalization, surgery and morbidity. Anything we can do to mitigate the risk of conditions like osteoporosis and fractures for postmenopausal women is a positive step,” said James Barsi, M.D., clinical associate professor of Orthopaedic Surgery at Stony Brook University. “The data from this study is particularly meaningful because of the large number and uniformity of participants, and we hope it leads to more doctors having conversations with eligible patients about HRT as an option.”

Previous HRT studies have provided valuable insights, but many were constrained by small sample sizes and potential confounding. In this retrospective study—conducted over 2,000 days—researchers used the TriNetX Research Network to identify 137,484 participants younger than 60 with a documented menopause diagnosis within the last 20 years. Using one-on-one propensity score matching, participants were selected based on demographics, comorbidities, nutritional deficiencies, metabolic conditions affecting bone health, and the use of bone-modifying agents. Those with prior use of HRT, preexisting bone malformations, and previous fractures did not qualify. Participants were then divided into two equal cohorts with balanced baseline characteristics—one group having initiated HRT within one year of their menopause diagnosis and the other never using it.

Highlights of study findings include:

• During the five-year follow-up, the non-HRT group demonstrated a significantly higher risk of developing osteoporosis compared to the HRT group (OR 1.18, 95% CI 1.092– 1.284, p < 0.0001).
• For fractures, no significant difference was found between the groups at three years (RR 1.02, not significant), but the non-HRT group had 6% higher risk at five years (RR 1.06, p < 0.05) and 13% higher risk at max follow-up (RR 1.13, p < 0.05).

“The true power of this study was the large database that allowed us to compare a high number of patients with similar factors over time,” Dr. Barsi stated. “Given evidence that early HRT may improve bone health and reduce fracture risk later in life, perimenopausal and menopausal women are encouraged to discuss HRT with their gynecologists or primary care physicians.”

With more than 39,000 members, AAOS is the world’s largest medical association of musculoskeletal specialists. The organization advances musculoskeletal health by providing comprehensive education to help orthopedic surgeons and allied health professionals best treat patients in their daily practices. AAOS is the source for information on bone and joint conditions, treatments, and related musculoskeletal healthcare issues; and it leads the healthcare discussion on advancing quality.