Approaches to osteoporosis management differ between and within countries. In the UK, for example, approaches differ between those organizations that place the primary emphasis on cost-effectiveness (eg, the National Institute for Health and Care Excellence) and those that emphasize clinical need and appropriateness of therapy (eg, the National Osteoporosis Guideline Group). To date, clinical guidelines have largely avoided making specific comments on the type of treatment that might be appropriately chosen in any particular case, leaving this to the discretion of the clinician in consultation with the patient. However, a review conducted by my colleagues and I—published in Osteoporosis International—has drawn attention to two recent developments that are now impacting treatment considerations.

Superiority of Anabolic over Antiresorptive Treatments

The first development is the demonstration of a more rapid and greater fracture risk reduction of anabolic compared with antiresorptive treatments. For example, in a study of post-menopausal women with osteoporosis, teriparatide 20 μg once daily was superior to oral risedronate 35 mg once weekly for the outcomes of new vertebral fractures (56% reduction) and all clinical fractures (52% reduction).

In another head-to-head study, sequential treatment with romosozumab—a humanized antibody that binds sclerostin, increases bone formation, and suppresses bone resorption—for 12 months followed by alendronate for 12 months was more effective than alendronate alone for the same duration. Over 24 months, new vertebral fractures, clinical fractures, and hip fractures were 48%, 27%, and 38% lower, respectively, in the romosozumab arm than in the alendronate alone arm. Most of this advantage was apparent within the first 12 months.

High- & Very High Fracture Risk

The current use of fracture risk assessment tools, such as FRAX, permits the classification of risk into low and high; the second development we noted in our review is that the high risk group can be usefully sub-divided into high- and very high-risk categories (Figure). Very high fracture risk can be easily characterized in certain clinical settings; of particular interest is the acutely elevated risk of a subsequent osteoporotic fracture immediately after an index fracture. For example, in the case of hip fracture, 61% of subsequent fractures over 10 years will occur within the first 2 years. This “imminent risk” suggests that treatment given as soon as possible after fracture could avoid a higher number of new fractures compared with delayed osteoporosis treatment. Additionally, treatment with more rapidly effective agents would be mandated, with first-line treatment with an anabolic agent and subsequent use of inhibitors of bone turnover.

In the presence of a recent fracture, multipliers can be applied to FRAX probability estimates to take account of the fracture recency with the result that a very high risk of fracture may be identified. For example, in a 70-year-old woman in the UK, a clinical vertebral fracture that occurred within the past 2 years is associated with a 1.5-fold higher major osteoporotic fracture (MOF) probability (30%) than for a woman of the same age with a prior fragility fracture of uncertain recency (20%). Combinations of risk factors can also result in a very high risk classification. For example, at age 70, a combination of a family history of hip fracture with a prior fragility fracture of uncertain recency is also associated with a very high fracture risk (30%), suggesting that a first-line anabolic regimen might be preferred.

Reducing Burden

Targeting treatment based on fracture risk is increasingly accepted in guidelines.  Superiority of anabolic treatments over antiresorptives in rapidly reducing fracture risk suggests that further risk categorization of individuals into high and very high risk will aid selection of patients for first-line anabolic therapy. Such approaches in the modern management of osteoporosis should lead to greater reductions in the future burden of recurrent fractures.

References

Kanis J, Harvey N, McCloskey E, et al. Algorithm for the management of patients at low, high and very high risk of osteoporotic fractures. Osteoporos Int. 2020;31(1):1-12.
https://link.springer.com/article/10.1007/s00198-019-05176-3