Providing that the diagnosis of osteoporosis has been properly done and secondary forms of osteoporosis excluded, the treatment of osteoporosis includes non-pharmocological interventions and the use of anti-osteoporotic drugs with proven anti-fracture efficacy.
The preventable risk factors for osteoporosis and osteoporotic fractures include vitamin D insufficiency, low calcium intake, high risk for falling, smoking and alcohol intake.
Any non pharmacological intervention for risk factors for osteoporotic fractures has negligible costs and it might be associated with general health benefits (e.g.: recommending giving up smoking, or promoting some physical exercise). A calcium intake not lower than 1 gr per day should also be recommended to everybody with supplements being recommended only if this threshold is not met by diet. Vitamin D deficiency (25OHD < 50 nmol/L) is extremely common in the elderly and it should be corrected before commencing ant pharmacological intervention.
The aim of osteoporosis treatment is the prevention of fragility fracture. A pharmacological intervention is justified when the benefits (lowering fracture risk) outweigh both side-effects and economic costs of the treatment. The treatment threshold can nowadays be based on the risk of fracture which can be assessed with ad hoc algorithms. The best known is FRAX™ (http://www.shef.ac.uk/FRAX) which computes the 10-year probability of a major osteoporotic fracture (vertebral, hip or forearm) using femoral neck BMD and clinical risks such as age, sex, previous fracture, parent with fractured hip, current smoking, glucocorticoid use, rheumatoid arthritis, secondary osteoporosis, and excess alcohol intake. A pharmacological treatment is recommended when fracture risk is considered unacceptable (for example > 30% 10 year risk of major fracture), but this threshold may vary individually and depending on the wiliness to pay. The drugs registered in Europe for the treatment of postmenopausal osteoporosis includes those that decrease osteoclastic activity (bisphosphonates, denosumab, SERMs) and a single bone anabolic agent, teriparatide.
The anti-resorbers rapidly decrease osteoclastic activity and bone resorption. This is associated with a later decrease in osteoblastic activity and bone formation. Teriparatide rapidly increases osteoblastic activity and bone formation but again this is associated with a later increase also of osteoclastic activity and bone resorption. The lag time to new coupling between bone resorption and formation represents for both categories of treatments the therapeutic window, during which bone tissue is growing. Strontium ranelate slightly increases bone formation and inhibits bone resorption, by a mechanism that is still poorly understood.
Alendronate, risedronate and zoledronic acid have been the only agents registered for the treatment of glucocorticoid induced osteoporosis until the registration for the same condition of teriparatide, which has shown superior anti-fracture efficacy over alendronate.
The duration of treatment has become a matter of importance since the observation of side effects which might be related to treatment exposure.
The decision of discontinuing the treatment depends on the drug used and on the re-assessment of fracture risk after at least 3-5 years of treatment. A treatment course with Teriparatide must always be followed by therapy with anti-reabsorptive (e.g.: bisphosphonates). Denosumab should never be discontinued and, if that occurs, a treatment course with bisphosphonates should be considered in order to prevent the rebound of bone turnover. Discontinuation of estrogens, Raloxifene, Basedoxifene, Risedronate and Ibandronate is associated with the quick loss of the acquired benefits, and therefore the discontinuation should never exceed 6 months.
Treatment with alendronate and zoledronate is characterized by an important extended effect after treatment discontinuation. Thus, after 5 years of optimal adherence, a treatment discontinuation might be planned in low-risk patients (<30% according to DeFRA), but not in patients with previous severe fractures or in whom the risk remains high even after years of treatment.
Disclosure of Interest None Declared
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