National Research Project
“RISK/BENEFIT OF BISPHOSPHONATES IN OSTEOPOROSIS”
Participating Centre and principal investigator from Unit of Biostatistics, Epidemiology and Public Health
Osteoporosis is a systemic skeletal disorder characterized by low bone density and micro-architectural deterioration of bone tissue, with subsequent increase in bone fragility and susceptibility to fracture. The first mentioning of osteoporosis reflected a histological
The WHO estimates that osteoporosis currently affects more than 75 million people in Europe, Japan and the USA alone, with an estimated lifetime risk for wrist, hip and vertebral fractures of around 15%, very similar to that of coronary heart disease. The “Epidemiological Study On the Prevalence of Osteoporosis” conducted in Italy among 6,811 postmenopausal women aged 40 to 80 years and 4,981 men of 60 to 80 years revealed that 23% of women and 14% of men were affected by osteoporosis. Women demonstrated a 4-fold increased risk compared to men. Indeed, one of two women and one of eight men over 50 years reported at least one fracture during their lifetime. It is also well documented that: (1) previous fragility fracture, (2) prolonged corticosteroid treatment, (3) hysterectomy or premature menopause, (4) liver or thyroid disease, (5) body mass index (BMI) less than 19 kg/m2, (6) smoking status, and (7) history of falling represent the most common risk factors for osteoporotic fractures, as a result of a reduced BMD . Therefore, the treatment of osteoporosis focuses on the prevention of BMD loss or even on increasing BMD. Bisphosphonates (BP), such as zoledronic acid, pamidronate, risedronic acid, and alendronic acid, are agents whose main pharmacological action is to inhibit the bone resorption trough their effects on osteoclasts. They also seem to have antiangiogenic effects, and once they are incorporated into the bony matrix, degradation is minimal . As a consequence, they have various clinical indications, all related to diseases characterized by diminished bone mass and risk of fractures. Initially, their use was restricted to patients with metastatic bone malignancy secondary to breast, lung, or prostate cancer, or multiple myeloma. Their benefit in these conditions led to wider application for other bone pathologies, such as osteoporosis and Paget’s disease.
Evidence from clinical trials indicate that oral biphosphonates (BP) reduce the incidence of osteoporotic fractures by 33% to 60% with a safety profile similar to placebo. However, studies from clinical practice report a suboptimal adherence to BP therapy and a high incidence (5.5%-8.2%) of gastrointestinal (GI)-events. Spontaneous reporting also suggests an association between BP use and osteonecrosis of the jaws (ONJ), with incidence rates of 1.3% to 7% after intravenous use, and 0.01%to 0.34% after oral use in osteoporotic patients. Observational studies are needed to elucidate the risks/benefit profile of BP in the secondary prevention of osteoporosis.
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