Research & future therapies

Goal-directed evidence: treat-to-target

The 2024 ASBMR/BHOF task force position statement crystallized a decade of evidence into a practical framework. Its core findings:

• BMD predicts fracture — and BMD change predicts benefit. The FNIH/SABRE collaboration, pooling more than 50 trials, showed a strong relationship between treatment-related BMD increases and the magnitude of anti-fracture efficacy. Increases in total-hip and femoral-neck BMD explained a somewhat greater share of the anti-fracture effect than lumbar-spine BMD.
• The level achieved is a target. Trials of both antiresorptive and anabolic agents show an inverse relationship between the on-treatment BMD level and subsequent fracture risk — so a specific BMD (a T-score above −2.5, using total hip) is a rational goal.
• Order matters. Multiple studies confirm greater BMD gains — particularly at the hip — when an anabolic is given before an antiresorptive, versus the reverse.
• Probabilities can guide the first choice. Recent analyses estimate the chance of reaching a target from a given starting BMD with each drug — for example, with denosumab, a starting total-hip T-score of −2.7 yields roughly a 71% chance of exceeding −2.5 at three years, falling steeply at lower starting points; anabolic agents reach targets from lower baselines more often. This lets clinicians pick the initial agent by whether it can realistically reach the goal.

The practical upshot: rather than defaulting every patient to an oral bisphosphonate ("step therapy"), treatment is chosen to reduce risk rapidly for those at very high and imminent risk, and to reach a defined BMD target within a reasonable time. See how we apply this under Treatment.

New & emerging directions

Several threads are actively evolving:

• Optimizing anabolic use. Because the anabolic effect of teriparatide is largest in the first ~6 months, cyclic dosing has been studied to try to broaden that window; results to date show cyclic and standard regimens produce broadly similar BMD and trabecular-bone-score gains, without a clear advantage for cycling.
• Real-world comparative effectiveness. Beyond randomized trials, real-world analyses compare agents such as abaloparatide and teriparatide in everyday practice, adding data on how they perform outside trial conditions.
• Better targets and measures. Trabecular bone score and other quality measures are increasingly used alongside BMD to capture the microarchitecture that density misses (see Beyond BMD).
• Prevention across the lifespan. There is a growing push to shift from post-fracture treatment to a preventive model that engages bone health earlier — at menopause and before — rather than after the first break.