Bisphosphonates, analogues of
pyrophosphate, are potent inhibitors of osteoclast-mediated
bone resorption. They are used in the treatment of
Paget's disease of bone, hypercalcaemia and osteolytic
bone disease of
malignancy, primary and
secondary hyperparathyroidism, and in
osteoporosis.
Bisphosphonate treatment causes an early reduction in
bone resorption followed by a later reduction in bone formation. The early inhibition of
bone resorption induces a reduction in serum
calcium which leads to increased
parathyroid hormone (PTH), and subsequently an increase in
1,25-dihydroxyvitamin D. The
secondary hyperparathyroidism of
bisphosphonate treatment also leads to urinary
calcium conservation and
phosphaturia, and a reduction in serum
phosphate. The increase in the PTH following
bisphosphonate therapy is a response to the change in serum
calcium and can occur even when there is hypercalcaemia, and this can cause
confusion in the interpretation of PTH results. The hypocalcaemic response to
bisphosphonates is occasionally severe, especially in patients with
hypoparathyroidism. The recent elucidation of
bisphosphonate action at the cellular level on the
mevalonate pathway has led to interest in its effects on
lipoprotein metabolism, which may prove to be of clinical significance. Newer and more potent
bisphosphonates are currently undergoing clinical trials in malignant
bone disease and
osteoporosis, and will lead to further advances in the optimal management of these conditions.