Glucocorticoid Therapy and Bone Loss
Patients receiving long-term glucocorticoid therapy for conditions such as inflammatory bowel disease and rheumatoid arthritis are also at risk of developing drug-induced bone loss. This effect appears to depend on dose and duration of therapy. Most bone loss has been documented to occur during initiation of treatment, with eventual plateaus achieved within 6 months to 1 year of therapy. Atraumatic fractures involving the vertebrae and ribs are seen in 30% to 50% of patients receiving chronic steroid therapy.
There are several mechanisms associated with glucocorticoid-induced bone loss. Steroids decrease bone remodeling by inhibiting osteoblast maturation and subsequent bone formation. Glucocorticoid use causes a net negative calcium balance and increased bone resorption due to suppressed intestinal absorption of calcium in conjunction with increased renal calcium and phosphate excretion and subsequent decrease in renal tubular calcium resorption.
Even the frequent use of inhaled steroids has been associated with induced bone loss and a decrease in bone density. These findings have been confirmed in a recent study conducted in 209 premenopausal asthmatic women who frequently inhaled steroids. The subjects were divided into three subgroups — two that used inhaled steroids at different dosages and a control group that did not use steroids. Bone density was assessed over a three-year period. The two subgroups using inhaled steroids showed decreases in bone density, with greater bone loss associated with higher steroid doses.
The authors concluded that, while inhaled steroid use should not be discouraged in this patient population, careful attention should be given to ensure that patients receive adequate amounts of calcium and vitamin D. In addition, bone mineral density should be measured every six months so that alternative therapies and interventions can be considered before excessive bone loss occurs. Although this study involved females, the authors suggest that similar results could be expected in males receiving similar doses of inhaled steroids.
Anticoagulants and Bone Loss
Heparin Use: The development of osteoporosis has long been associated with chronic heparin therapy. The mechanism for heparin-induced osteoporosis has not yet been established, although several theories have been postulated. Some theories include abnormalities in vitamin D metabolism, enhanced osteoclast activity and diminished osteoblast activity. Patient complaints of back pain, in addition to vertebral compression fractures and a decrease in bone mineral density, have been documented. The severity of osteoporosis has been associated with the duration as well as the daily dose of heparin. Research by Rupp, et al. and Griffith, et al. places patients receiving doses greater than 30,000 units per day for more than three months at greater risk. Treatment typically involves discontinuation of heparin. Both unfractionated and the new low molecular weight (LMW) heparin products have been implicated, although animal studies suggests a lower incidence of osteoporosis with LMW heparin.
Warfarin Use: Heparin is the not the only anticoagulant associated with bone disease. Chronic therapy with warfarin has been associated with bone loss via a reduction in carboxylated fragments of osteocalcin — the major noncollagenous protein contained in bone. The normal metabolism of vitamin K involves gamma carboxylation of osteocalcin, which maintains bone growth. Knaper and colleagues noted a reduction in bone turnover among postmenopausal women receiving supplemental vitamin K. This contradicted research by Rosen, et al., who reported no difference in skeletal integrity in adults receiving long-term warfarin versus controls.Additional research is warranted to determine the significance of warfarin-associated bone loss.
Thyroxine and Bone Loss
Excessive therapy with thyroxine has also been associated with bone loss. Thyroid supplements are one of the most frequently prescribed medications; more than 10% of postmenopausal women receive thyroid hormone replacement. Euthyroid patients receiving suppressive thyroxine therapy are also at risk.As with other cases of drug-induced bone disease, dose and duration of therapy are implicated.Exogenous hyperthyroidism-induced bone loss is due to increased bone resorption, subsequent decreases in PTH, and increases in ionized calcium. Maintaining thyroid hormone replacement at physiologic doses appears effective in minimizing bone loss due to therapy.