Effects of disodium dichloromethylene diphosphonate on bone loss in paraplegic patients.

Abstract

A B S T R A C T 21 paraplegic patients with recent traumatic spinal cord injury were orally administered 400 (n = 7) or 1,600 (n = 7) mgld of disodium dichloromethylene diphosphonate (Cl2MDP) and compared with a placebo group (n = 7) to test the preventive effects of the drug on acute bone loss and osteoclastic resorption. C12MDP therapy was initiated at a mean of 17.6 d after the onset of paraplegia. The study lasted at least 6 mo, consisting of a 3.5-mo treatment period, and a variable follow-up period. The effects of C12MDP were assessed by blood and urine biochemistry, bone histomorphometry on transilial samples, photon absorptiometry of the tibia and fibula, and radiomorphometry of the femur. The elevation in serum and urinary calcium and in urine hydroxyproline observed in the placebo group did not appear under treatment. With both doses of C12MDP there was no further decrease in the bone mineral content. In the treated groups, a smaller percentage increase in osteoclastic population was also noted when compared with the placebo group, but this difference was not significant. There was no mineralization defect induced by C12MDP, as shown by tetracycline double labeling. It thus appears that at doses ranging between 400 and 1,600 mg, given as early as possible, C12MDP can prevent or reduce the development of the acute bone loss of paraplegic patients, without adverse side effects, though it does not prevent the development of heterotopic ossification.

Bone loss in spinal cord-injured patients: from physiopathology to therapy

“…3 During the first months following injury, the releasing of the mineral phase modifies calcium homeostasis. 37,38 Hypercalcemia and hypercalciuria, [37][38][39][40] which lead to the development of renal calculi 41 and to alterations in the calciotropic hormonal profile, 2,3,38,[42][43][44] are the most commonly encountered abnormalities. Histomorphometric data demonstrated that the principal cause of bone loss is the increase in bone resorption as defined by an augmentation in eroded surfaces and of the number of osteoclasts.…”

Demineralization in tetraplegic and paraplegic man over time

“…Early studies primarily measured BMC at the distal radius 1,2 or at the iliac crest. 3,4 Later studies included either BMC or BMD measurements of the lower extremeties. 5 ± 12 These studies were performed on small patient populations and did not take into account the length of time of injury nor the age of the patient.…”

Bone mineral content of the lumbar spine and lower extremities years after spinal cord lesion

“…The two early studies primarily measured BMC corresponding to the distal radius (Bergmann et al, 1977-78;Griffiths et al, 1972), while the two more recent studies included BMC measurements of the lower extremities in the course of a therapeutic trial (Minaire et al, 1981, Phillips et al, 1984.…”