Post-Transplant Bone Disease

By Leslie Spry MD FACP FASN

The risk for fracture after kidney transplantation is estimated conservatively at 2 to 3% of patients per year1.  Mineral and bone disorder of chronic kidney disease (CKD-MBD) is a common outcome after transplantation.  For those with special interest, there is a recent comprehensive review of CKD-MBD in transplantation found in the recently published KDIGO Clinical Practice Guideline2.

Normal bone consists of minerals such as calcium and phosphorus that are deposited in a framework known as collagen matrix.  The cells in bone are osteoclasts (bone eaters) and osteoblasts (bone builders).  Important factors that contribute to bone cell activity are parathyroid hormone, vitamin D, blood levels of calcium and phosphate, and bone turnover markers such as alkaline phosphatase.  Age is also a major factor, as bone density builds to a maximum in early adulthood and then gradually declines.  Gender is important as ladies build less bone than men and start to decrease bone density sooner than men.  Women are more likely to suffer low bone density, also known as osteopenia and osteoporosis.  Bone is continuously being torn down (eaten) and regenerated (built up) in a process known as re-modeling.

Patients with chronic kidney disease suffer from CKD-MBD.  As kidneys fail and dialysis is initiated, levels of calcium and phosphorus in the blood change and lead to an accumulation of parathyroid hormone.  This is known as secondary hyperparathyroidism.  Excess acid in the blood (a low blood carbon dioxide) leads to bone disease.  Patients with CKD-MBD may have combinations of bone disease that include thin and weak bone.  Thus, patients who get a kidney transplant start with a variety of bones diseases, which are unique to each individual.  Patients with a kidney transplant may have less than perfect function after the transplant and thus may still develop CKD-MBD as a consequence of poor and worsening kidney function. 
Common findings in the early months after kidney transplantation include persistent secondary and tertiary hyperparathyroidism, increased serum calcium, low serum phosphate, and vitamin D deficiency.  Studies show that there is substantial loss of bone in the first year after transplantation.  This loss may be as a consequence of transplant drug treatments such as steroids.  Bone loss can also be due to deficiencies of vitamin D, continued secondary hyperparathyroidism, and impaired physical activity.

In the early transplant period (within 3 months), it is advisable to measure the bone mineral density by measurement using a DEXA bone scanner or other device for measuring bone density.  If there are scans available from measurements prior to transplantation, this will give your physician information that will allow decisions to be made about any necessary treatment.  If your kidney transplant is functioning poorly with an estimated glomerular filtration rate (eGFR) of less than 30, then further testing may not be helpful.  If your eGFR is greater than 30, measurement of bone density every 2 or more years will be helpful in designing treatment programs that make sense.  If you have risks such as diabetes, a post-menopausal female, have established low bone density, have a strong family history of osteoporosis or fractures of the spine, take steroids, or have back pain as a continuing symptom, then bone testing may be advisable after transplantation.

Unfortunately, there are not many studies to guide recommendations for treatment of bone disease after transplant.  Testing of calcium, phosphorus, vitamin D, alkaline phosphatase and parathyroid hormone at intervals may be helpful in guiding treatment.  Your nephrologist is best at interpreting this information and guiding treatment.  The most common and effective treatment is to make sure calcium and vitamin D supplementation are sufficient to correct levels.  If bone density is very low, treatment with bisphosphonates such as alendronate, risedronate, or ibandronate may be helpful, especially if the eGFR is above 30.  Regular physical activity is necessary to create and maintain healthy bones.

A peculiar type of bone pain that occurs in joints after transplantation known as “post-transplant distal limb syndrome” that is a self limited disorder causing intense pain in the joints in the first few months after transplantation.  It usually resolves with rest and relief of pain within several weeks3.

Bone health needs to be monitored carefully after transplantation and is an important component of your after transplant care.  Treatment is very complex.

References:

  1.  Weisinger JR, et al.  Bone disease after renal transplantation.  Clin J Am Soc Nephrol 2006; 1: 1300 – 1313
  2. Kidney Disease: Improving Global Outcomes (KDIGO) CKD-MBD Work Group. KDIGO clinical  practice guideline for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). Kid Int 2009; 76 (Suppl 113): S1-S130
  3. Tillmann FP, et al. Post-transplant distal limb syndrome: Clinical diagnosis and long-term outcome in 37 renal transplant recipients. Transpl Int 2008; 21: 547-553