Bone Density Loss - 4
PART 2
However, after 12 months of calcium at 500 mg/d and calcitriol at 0.5 mcg/d, no trend toward further bone loss was noted. However, after 12 months of alendronate therapy at 10 mg/d plus calcitriol at 0.5 mcg and calcium at 500 mg, bone density increased 5% at the LS spine and 4% at the femur. A recent study demonstrated that the rapid, severe bone loss associated with heart transplantation could be attenuated by either of 2 preventive regimens. Both nasal salmon calcitonin at 200 U/d with continuous calcitriol at 0.5 mcg/d or intermittent pamidronate at 0.5 mg/kg intravenously every third month were equally effective by 18 months, although pamidronate slowed bone loss more initially (Bianda, 2000). A randomized, controlled clinical trial comparing oral clodronate with intranasal calcitonin for the treatment of low bone mass in 46 patients with osteopenia or osteoporosis after kidney transplantation found that both treatments improved BMD at the LS spine. No adverse effect on graft function was noted, although biochemical exacerbation of secondary hyperparathyroidism was docu mented (Grotz, 2001). To date, limited data suggest that pretransplant treatment with bisphosphonates decreases posttransplant fracture risk. If administered prior to liver transplant, intravenous pamidronate prevents osteoporotic vertebral collapse (Reeves, 1998; Bishop, 1999). Similarly, a recent prospective, uncontrolled pilot study using intravenous pamidronate in lung transplant recipients decreased the fracture rate and preserved bone mass at 1-year posttransplantation. The authors urged that bisphosphonate therapy be started before transplant surgery is contemplated (Cahill, 2001). Transdermal estrogen therapy protects postmenopausal women with liver transplants from osteoporosis, similarly to healthy postmenopausal women (Isoniemi, 2001). Estrogen is also known to improve BMD in women receiving glucocorticoids and to prevent CsA-mediated bone loss in animals. If estrogen is prescribed together with progesterone, fixed daily doses are preferred over cyclic regimens because estrogen can enhance the hepatic metabolism of cyclosporine, resulting in erratic blood levels. Estrogen alone is probably insufficient to prevent transplant-induced bone loss, particularly in the first year following transplantation (Shane, Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism, 1999). Consultations: Given the medical complexity of the typical patient awaiting solid organ transplantation, a referral to an endocrinologist or bone metabolism expert should be considered. Diet: Patients should avoid cigarette smoking and heavy alcohol consumption, both of which are associated with negative bone balance. Activity: Regular weight-bearing and muscle-strengthening exercises are recommended to reduce the risk of fracture (when medically possible) as first-line therapy for osteoporosis. Improving overall fitness is recommended to minimize the risk of falling.
MEDICATION
Any patient who meets WHO criteria for low bone mass (osteoporosis) should receive pharmacologic treatment similar to any other patient with osteoporosis or osteopenia. Vitamin D and calcium alone are clearly insufficient to prevent transplant-related bone loss. Postrenal transplant bone disease reflects the complexity of preexisting renal osteodystrophy, although many aspects of renal osteodystrophy improve with transplantation. Hyperparathyroidism may persist in a subset of patients.
Drug Category: Bisphosphonate derivatives -- These agents prevent steroid-induced bone loss and are drugs of choice if not medically contraindicated. Their oral bioavailability is limited. Because bisphosphonates are associated with a fall in serum phosphate and calcium levels and a secondary rise in intact PTH levels, they may prolong the time to resolution of secondary hyperparathyroidism. Bisphosphonates bind to the surface of bone and are slowly removed over years during bone remodeling. Effects on development are unknown, and they have the potential to be released from maternal bone and be transferred to the skeleton of the fetus. Bisphosphonates are not approved for use in children. Some authors believe that bisphosphonates are not appropriate for women of childbearing age (Dawson-Hughes, 2001).
Alendronate (Fosamax) and risedronate (Actonel) are both indicated for prevention and treatment of osteoporosis and steroid-induced osteoporosis. These agents increase BMD at the hip, spine, and whole body; they reduce new vertebral fractures and new hip fractures. Clinical experience suggests that a significant number of patients experience upper GI disturbance, particularly esophageal symptoms (eg, chest pain, heartburn, painful or difficult swallowing), although the incidence of adverse effects with either dose is no different from
placebo in clinical trials. A rare reported complication of alendronate (probably <1%) is esophageal ulceration. Use caution when prescribing these agents for patients with esophageal dysmotility, stricture, or history of prior upper GI hemorrhage (Sharpe, 2001; Umland, 2001).
Drug Name Alendronate (Fosamax) -- Inhibits bone resorption via actions on osteoclasts or osteoclast precursors. Should be taken with a large glass of water, at least 30 min before eating and drinking, to maximize absorption. Because of possible esophageal irritation, patients must remain upright after taking medication. Because it is renally excreted, it is not recommended in patients with moderate-to-severe renal insufficiency, ie, CrCl <30 mL/min or CrCl >3 mg/dL; thus, use in perirenal transplantation is limited. Adult DoseProphylaxis: 5 mg PO qd Treatment: 10 mg PO qd; alternatively, 70 mg PO qwk Pediatric DoseNot established Contraindications Documented hypersensitivity; hypocalcemia, esophageal abnormalities, inability to stand upright for 30 min InteractionsNone reported PregnancyC - Safety for use during pregnancy has not been established. Precautions Must be taken at least 30 min before first food, beverage, or medication of the day and should be taken with a large amounts of water; caution in renal impairment
Drug Name Risedronate (Actonel, Actonel 35 mg Once-A-Week) -- Potent aminobisphosphonate. Inhibits bone resorption via actions on osteoclasts or osteoclast precursors. Take 30 min before first food or drink of the day, other than water. Adult Dose5 mg PO qd; alternatively, 35 mg PO qwk Pediatric DoseNot established ContraindicationsDocumented hypersensitivity, hypo calcemia, and renal impairment InteractionsNone reported PregnancyC - Safety for use during pregnancy has not been established. PrecautionsMonitor hypercalcemia-related parameters (eg, serum levels of calcium, phosphate, magnesium, potassium); maintain adequate intake of
calcium and vitamin D to prevent severe hypocalcemia; caution in active upper GI problems; not for concomitant administration with alendronate for osteoporosis in postmenopausal women; adverse effects include diarrhea, headache, and arthralgia
Drug Category: Endocrine agents -- May inhibit osteoclastic bone resorption.
Drug Name Calcitonin (Miacalcin, Calcimar, Cibacalcin, Salmonine) -- Inhibits bone resorption. Approved by FDA for treatment of osteoporosis, but not for treatment of steroid-induced osteoporosis (Fudman, 1997). SC administration is also available but used less commonly. SC form may have some analgesic effect in patients with fractures. Results from a single, controlled clinical trial indicate that it decreases osteoporotic vertebral fractures by approximately 40% (Chestnut, 2000). Overall, efficacy data for calcitonin are weaker than for either HRT or bisphosphonates. No evidence indicates that calcitonin decreases risk of hip fracture.Generally considered a safe but significantly less effective intervention for osteoporosis. May be used as an alternative to HRT or bisphosphonates for patients who meet criteria for treatment but who are unwilling to take them or who have found treatment unsuccessful (Silverman, 2001). Attenuates glucocorticoid-induced bone loss and may be useful in the posttransplantation period if bisphosphonates are contraindicated or not tolerated. Animal data suggest that calcitonin can mitigate CsA-mediated bone loss (Epstein, 1996). Adult Dose200 U intranasally into one nostril qd; alternate nostrils each day Pediatric DoseNot established ontraindicationsDocumented hypersensitivity Interactions None reported PregnancyC - Safety for use during pregnancy has not been established. Precautions Hypocalcemia may occur; examine urine sediment during prolonged therapy
Further Inpatient Care:
If an antiresorptive agent such as Fosamax (alendronate) is used, significant increases in spine BMD can be observed within 1 year. However, an average of 4-5 years may b needed to see a change in femoral-neck BMD with alendronate or risedronate, probably longer with weaker antiresorptives. In the transplant recipient, annual assessments of BMD by DEXA scanning are prudent. Any clinical suggestion of fracture should prompt bone radiographs. (SOURCE: E- MEDICINE http://www.emedicine.com/med/topic3481.htm)
