The etiology of fractures is multifactorial, including factors that increase the risk of bone fragility and the risk of falls. In terms of bone fragility, the final pathway is the degree and balance of bone turnover and the quantity, structural distribution and quality of the remodeled bone. Treating osteoporosis means preventing a first or subsequent fracture in patients who have been identified to be at high risk for fractures. Fracture prevention can be summarized using a 5-step approach (figure).
The first step is case finding: which subjects/patients deserve attention for fracture risk evaluation? These include patients with a recent fracture (increasingly evaluated in the context of a Fracture Liaison Service), patients with diseases (e.g. inflammatory rheumatic diseases) or medications (e.g. glucocorticoids) that are known to increase the risk of fractures, and subjects with an accumulation of other risk factors for fracture.
The second step is risk evaluation, for which bone densitometry, imaging of the spine and evaluation of the presence of risk factors (as found in the FRAX and Garvan algorithms) are available.
Once a patient at high risk for fracture is identified, the third step is differential diagnosis for underlying diseases using medical history, clinical examination and laboratory tests.
In the fourth step, medical therapy consists of instructing the patient about life style, fall prevention, ensuring sufficient calcium and vitamin D intake and discussion of the possibilities of medication. The choice of drugs is based on the spectrum of demonstrated fracture prevention (vertebral, non-vertebral and hip fractures), route (oral, SC, IV) and frequency of administration (from daily to yearly two times or once) and safety profile. Anti-resorptive drugs (bisphosphonates, denosumab, SERMs), that decrease high bone turnover, are a major approach for fracture prevention. In patients with severe osteoporosis, or having new fractures despite adequate anti-resorptive drug treatment and in patients with low bone remodeling, such as in glucocorticoid osteoporosis, osteo-anabolic treatment (recombinant human PTH fragment teriparatide) should be considered.
The fifth step is follow-up for checking compliance, tolerance and efficiency, and to decide about duration of treatment.
Possible new treatment options include odanacatib, a specific inhibitor of cathepsin-K, the main collagenase of the osteoclast, for which the results of a phase III clinical trial are on the way, and anti-sclerostin antibodies that stimulate bone formation and that are studied in phase II-III clinical trials.
Disclosure of Interest P. Geusens Grant/research support from: Pfizer, Abbott, Lilly, Amgen, MSD, Will, Roche, UCB, BMS, Novartis, Consultant for: Amgen, Speakers bureau: Pfizer, Abbott, Lilly, Amgen, MSD, Will
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