Osteoporosis, other bone disorders
The bisphosphonates reduce the risk of fracture in osteoporosis and should be used for the treatment of established postmenopausal osteoporosis. The dose regimen of each varies depending on the strength and formulation of the bisphosphonate, some being taken on a daily basis, weekly, cyclically for two weeks every three months, monthly or yearly. It is important to check these regimens before prescribing.
Rarely, bisphosphonates are associated with osteonecrosis of the jaw. Cases are usually associated with dental procedures and with concomitant risk factors such as cancer, chemotherapy, radiotherapy, treatment with corticosteroids or angiogenesis inhibitors, smoking, a history of dental disease, and poor oral hygiene. The risk is increased by intravenous administration and is highest with zoledronate. Bisphosphonates can also cause rare atypical femoral fractures (often bilateral), particularly when used long-term. The need for continued therapy should be periodically reassessed based on risks and benefits to the individual patient, particularly after 5 years of treatment.
The selective oestrogen receptor modulator raloxifene is indicated for the treatment and prevention of osteoporosis in postmenopausal women. A significant reduction in the incidence of vertebral, but not hip, fractures has been demonstrated. Raloxifene increases mineral density in bone, reduces cholesterol levels and reduces the risk of endometrial or breast cancer. It may induce flushing and is associated with a similar increased incidence of thromboembolic events as HRT.
Strontium ranelate is described as a dual action bone agent as it brings about bone remodelling by both inhibiting bone resorption and increasing bone formation. Its dual mechanism of action involves the stimulation of pre-osteoblast replication, leading to increased bone matrix synthesis, and inhibition of osteoclast activity and differentiation, leading to reduced bone resorption. It increases trabecular bone mass, trabeculae number and thickness, and bone mineral density, improving bone strength and thereby reducing the risk of vertebral and hip fractures.
Denosumab is a monoclonal antibody that targets the RANK ligand to specifically inhibit the development, function and survival of osteoclasts. It increases bone density and reduces osteoporotic fractures. Like the bisphosphonates, denosumab is associated with a rare risk of osteonecrosis of the jaw and atypical femoral fractures, and the need for continued therapy should be periodically reassessed based on risks and benefits to the individual patient, particularly after 5 years of treatment.
Calcitonin (salmon) maintains bone mass and is indicated for the treatment of Paget's disease, hypercalcaemia of malignancy and to prevent bone loss due to sudden immobilisation. Calcitonin inhibits bone resorption by a direct action on osteoclasts, inhibiting their activity and reducing bone turnover.
Calcium requirements are raised during the years following the menopause. During the first 5 postmenopausal years women lose about 2% of their bone mass per year, dropping to 1% per year thereafter. Calcium supplements can be used to prevent bone loss when dietary intake is low. Evidence indicates that vitamin D3 is also important. Oral calcium can be given in the form of various calcium salts (carbonates, citrates, gluconates, lactates, phosphates). All the salts are readily absorbed from the GI tract and there is little to choose between them. In patients with achlorhydria, calcium salts should be taken with food to maintain absorption. Alternatively, calcium citrate may be preferable, as its absorption is independent of gastric acid secretion. All calcium supplements can cause irritation of the GI mucosa and should be used with caution in patients with GI obstruction or ulcer.