By Bruce Long, MD
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If you have a busy rheumatology practice, don’t be surprised if one of your next patients is an organ transplant recipient or candidate asking for advice about a related complication such as osteoporosis. According to the U.S. Department of Health and Human Services, 79 Americans receive organ transplants every day. More than 400 organ transplants are performed yearly at Cleveland Clinic. For patients with end-stage organ failure, transplantation is now a well-accepted option for a second chance at life
Changes in bone health in transplant recipients may not present as dramatically as a cyclosporine-related gout attack, but they are still serious, can develop rapidly and may lead to osteoporosis with resulting fractures, debility and death. Interventions to optimize bone health in organ transplant recipients enhance these patients’ survival and quality of life.
Many Reasons for Increased Bone Risk
The reasons for low bone mass in transplant recipients include factors present before transplant, such as those associated with the underlying disease, inflammation, treatments and chronic illness, as well as post-transplant factors, most notably anti-rejection medications.
People ill enough to need an organ transplant often already have significant bone disease (see list for examples). In addition, transplant candidates are generally too sick for vigorous physical activity, so they miss out on exercises to promote balance and bone strength. Of course, the traditional osteoporosis risk factors ‒ age, family history, hormonal status, nutrition, and other secondary diseases and medications ‒ may further contribute to low bone mass. Prior osteoporosis could even affect the transplant procedure. The kyphosis or loss of rib-to-pelvis space from multiple vertebral compression fractures can, if severe enough, prevent the allograft from fitting in the available space.
The most commonly used anti-rejection medicines that adversely affect bone are prednisone, tacrolimus and cyclosporine. Based on experimental models, mycophenolate mofetil, azathioprine and sirolimus are not thought to cause bone loss.
Glucocorticosteroids adversely impact bone in several ways. They stimulate osteoclasts, inhibit osteoblasts, increase apoptosis of osteoblasts and osteocytes, decrease gonadotropins, reduce calcium intestinal absorption and enhance renal calcium excretion. Glucocorticosteroids’ effect on bone loss is most pronounced in the first few months of use
The contribution of tacrolimus or cyclosporine to bone loss in humans is less clear, as any effect is confounded by the fact that these agents are often given with prednisone. Studies have been largely confined to experimental animals. Both tacrolimus and cyclosporine are calcineurin inhibitors whose effects are mediated by T lymphocytes. In rat models, there is rapid cancellous bone loss after exposure to these drugs.
Cleveland Clinic’s Approach
At our Center for Osteoporosis and Metabolic Bone Disease, we like to see patients before their transplant and as needed thereafter to optimize their bone health. This includes a visit shortly after the transplant to make sure they are on a good bone health program, because bone mass can decline rapidly in the first year after transplant.
We begin with a history and physical exam followed by bone mineral density (BMD) measurement of the spine and hip by dual-energy X-ray absorptiometry (DXA) (Figure 1). Key points of the history include assessment of risk factors for osteoporosis and falls ‒ based on a review of medications, a detailed dietary calcium evaluation and assessment for underlying conditions associated with metabolic bone diseases ‒ and consideration of other risk factors or past events that would influence choice of anti-resorptive or anabolic agents.
Figure 1. A patient undergoing dual-energy X-ray absorptiometry
During the exam, we especially evaluate height, posture, spinal configuration, balance, strength and signs of previous fractures or of underlying metabolic conditions that may affect bone. The latter include overactive thyroid, hypogonadism, connective tissue disorders and inflammatory diseases. Additional studies are influenced by the underlying disease state and risk factors but usually involve a blood count and chemistry panel to assess calcium and alkaline phosphatase levels; renal, liver and thyroid function; and levels of phosphorus, parathyroid hormone, vitamin D, serum markers of bone formation and urine markers of bone degradation. We discuss bone physiology and how the patient’s disease and risk factors may contribute to changes in bone status, as well as the transplant’s likely effect on bone.
The individual’s bone health therapy depends on the needs identified from this assessment. Most patients need calcium and vitamin D supplements, although dietary calcium intake must be accounted for to avoid prescribing excessive amounts.
We usually recommend a weight-bearing exercise program and, if needed, therapies to improve strength and balance. If the BMD measurement reveals osteoporosis, or if the patient has a history of fragility fractures, is taking a significant glucocorticosteroid dose or has other significant risks, we add an appropriate anti-resorptive or anabolic medication after discussing its use and potential side effects with the patient.
Our priority is to maintain the quality of life for these transplant patients who have been given a second chance. Because of the threat that osteoporosis can pose, the early interventions we offer to optimize bone health make our center an integral part of these patients’ care team.
Dr. Long, a staff physician in the Center for Osteoporosis and Metabolic Bone Disease, has an interest in bone disorders of organ transplant patients.