By Ramsey Hachem, M.D.
Washington University School of Medicine Barnes-Jewish Hospital
Division of Pulmonary and Critical Care
February, 2010
Osteoporosis is a skeletal condition characterized by a reduction in bone mineral density and alterations in bone architecture and consistency resulting in an increased risk of fractures, including spontaneous ones. Osteoporosis is an important medical complication for the trasnplant patient because the immunosuppressive regimen, particularly prednisone and steroids in general, contribute to bone loss. The World Health Organization (WHO) defines osteoporosis as bone mineral density 2.5 standard deviations below peak bone density. Normally, the bony matrix is continually being remodeled, but the fundamental problem in osteoporosis is an imbalance between bone formation and resorption that results in decreased bone density over time. The diagnosis of osteoporosis is established by measuring bone mineral density using a radiology test called dual energy x-ray absorptiometry, or DEXA scan.
In general, post-menopausal women have the highest risk of osteoporosis, but the disorder can affect men and women of all ages. A significant proportion of patients have osteoporosis before transplantation because of chornic steroid use, low body weight, smoking history, physical inactivity, and vitamin D deficiency. Other predisposing factors include malnutrition and malabsorption of vitamin D, especially in patients with cystic fibrosis. In severe cases, osteoporosis may sometimes be a contraindication to transplantation since it is expected to worsen after transplantation. This is especially true if the patient has had multiple vertebral compression fractures or a hip fracture since these can be very disabling.
Therefore, prevention and treatment of osteoporosis are criticial to better bone health. Non-medical therapy is a straightforward but essential component of treatment. This includes a healthy diet with adequate supllies of calcium and vitamin D. The total recommended amount of calcium is 1500 mg daily; this includes dietary intake and supplemental calcium. The recommended amount of vitamin D is 800 IU daily, but higher doses are necessary if the patient has malabsorption or is vitamin D deficient. Weight-bearing exercise is another important non-pharmacologic treatment of osteoporosis. The minimum recommended exercise regimen to derive a benificial effect is 30 minutes three times weekly. In a large study of post-menopausal women, those who exercised 4 hours per week had a 40% lower risk of hip fracture than those who exercised less than an hour a week. Smoking cessation is strongly recommended for everyone in general, but smoking also accelerates bone loss. This is an additional risk factor for osteoporosis among past smokers. These measures should be adopted for all patients who have osteoporosis or are at increased risk for the disorder. However, these lifestyle modifications alone are not sufficient for those who have osteoporosis and an increased risk of fractures. Such patients require pharmacologic therapy for osteoporosis.
Bisphosphonates are a class of drugs that inhibit bone resorption and are widely used for the prevention and treatment of osteoporosis. This class of drugs includes alendronate, risedronate, and ibandronate, among others. By inhibiting bone resorption, they increase bone mass and reduce the risk of fractures. Numerous randomized controlled trials have demonstrated significant reductions in the risk of fractures for these drugs when compared to placebo. Bisphosphonates are poorly absorbed when taken orally and must be taken on an empty stomach. Additionally, the drug should be taken with at least 8 ounces of water, and the patient should stay upright for 30-60 minutes to reduce the risk of esophagitis.
Many patients have hypogonadism before transplantation as as result of chronic illness, malnutrition, or prednisone use, and this contributes to the risk of bone loss. Unless contraindicated, hormonal replacement with testosterone for men and estrogen-progestin for women can alleviate bone loss. However, the use of estrogen is no longer considered a first-line treatment for osteoporosis among post-menopausal women because of an increased risk of cardiovascular disease and breast cancer. Another class of hormonal agents, known as selective estrogen receptor modulators, include raloxifene and tamoxifen. These do not have the same risk profile as estrogen, but can be effective for osteoporosis prevention although their efficacy is inferior to bisphosphonates. Unlike other agents that inhibit bone resorption, teriparatide (Forteo) is a parathyroid hormone that stimulates bone formation and reduces the risk of fractures. It is administered as a daily injection. However, its use is limited to a maximum of two years because an increased risk of bone cancer was noted in animal studies, although this has not been observed in humans.
Osteoporosis is a serious condition that can result in disabling symptoms and adversely affect quality of life after lung transplantation. However, lifestyle modifications and medical therapy can improve bone health and mitigate the impact of osteoporosis on outcomes after transplantation.