eMedicine Specialties > Endocrinology > Metabolic Bone Disease

Osteoporosis in Solid Organ Transplantation: Treatment & Medication

Author: Carmel M Fratianni, MD, FACE, Associate Professor of Clinical Medicine, Department of Internal Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Southern Illinois University School of Medicine
Contributor Information and Disclosures

Updated: May 20, 2009

Treatment

Medical Care

Because chronic pain and immobilization from fractures can significantly diminish quality of life, it has been recommended that patients with extremely low bone mass or osteoporotic fractures documented prior to transplant be counseled about the increased fracture risk that follows transplantation.73 Since an entirely normal bone density pretransplantation is not protective against posttransplantation fracture, prophylaxis against bone loss should be given in all transplant recipients, without regard to baseline bone density.59

The aim of medical therapy should be to prevent bone loss and (if possible) to restore bone lost before transplantation. Guidelines established by the American College of Rheumatology and the UK Consensus Group74,75 recommend that patients who receive daily glucocorticoid at doses of 7.5 mg of prednisolone or more for 6 months or longer should begin preventive therapy. Transplant recipients clearly meet this criterion.

Advise all patients to maintain an adequate total elemental calcium intake (ie, 1000-1500 mg) and to take supplements as necessary. The dose of supplemental calcium should be individualized based on dietary calcium intake, menopausal status, and underlying medical issues. For example, a pharmacologic dose of calcium administered to a renal transplant recipient with persistent secondary hyperparathyroidism could worsen hypercalciuria because of excess PTH action and could be contraindicated.

Administer vitamin D at 400-1000 IU/d to all patients. However, patients with malabsorption, cystic fibrosis, or PBC have higher vitamin D requirements,4,76 and 25-hydroxyvitamin D levels should be monitored to assess the adequacy of replacement.

Parent vitamin D at doses of 400-1000 IU daily is insufficient to prevent posttransplant osteoporosis. Active metabolites of vitamin D are more promising in this regard and may work by improving intestinal calcium absorption and directly or indirectly suppressing PTH secretion.77

Calcidiol (25-hydroxyvitamin D)

In an uncontrolled 12-month study, Talalaj administered calcidiol in 77 renal transplant recipients. Subjects received calcidiol 40 mcg with calcium 3 g daily. In the untreated group, BMD significantly decreased, by 7.1% at the LS spine and 5.5% at the femur neck, while BMD remained stable at the LS spine (–0.2%) or modestly increased at the femur neck (1.3%) with calcidiol. A significant decrease in vertebral deformities was notable in the calcidiol group.78

Randomization immediately following cardiac transplant to 32,000 IU per week of oral calcidiol for 18 months increased LS spine BMD, compared to etidronate or nasal calcitonin, which were associated with a decrease in LS spine BMD.79

Alfacalcidol (1-alphahydroxyl vitamin D)

1-Hydroxylated vitamin D may be of particular use in clinical situations associated with accelerated bone loss. There is evidence that alfacalcidol increases trabecular BMD and prevents vertebral fracture. In newly postmenopausal women, alfacalcidol at 1 mcg/d prevented the accelerated loss of vertebral BMD over 3 years following the onset of menopause.

In a nontransplant population of patients with established glucocorticoid-induced osteoporosis, Ringe et al compared the therapeutic efficacy of alfacalcidol with parent vitamin D-3 in patients requiring long-term glucocorticoids. Matched pairs were randomized to 1 mcg alfacalcidol with 500 mg calcium per day (n=103) or 1000 IU of vitamin D-3 with 500 mg calcium per day (n=101). The median percentage increase in spine BMD in the alfacalcidol group (+2.4%) was 4-fold greater than the parent vitamin D group (-0.8%) over 3 years. An impressive 52% relative risk reduction in new fractures over 3 years was demonstrated with alfacalcidol; approximately 41% of patients treated with parent vitamin D sustained a new fracture over 3 years, compared with only approximately 19% of those treated with alfacalcidol. In addition, alfacalcidol decreased back pain to a greater degree than plain vitamin D-3.

Generally, side effects in both groups were mild, and only 3 patients in the alfacalcidol group and 2 in the vitamin D group had moderate hypercalcemia. Alfacalcidol would appear to be superior to plain vitamin D-3 in the treatment of established glucocorticoid induced osteoporosis. At 0.5-1 mcg daily, others have found it useful in preservation of spinal bone density in rheumatoid arthritis as well as transplant osteoporosis, although liver and lung transplant recipients responded more favorably than cardiac transplant recipients.80

In cardiac transplant recipients, spine and femoral bone loss were decreased with alfacalcidol plus calcium. Moreover, fewer vertebral fractures were seen in alfacalcidol-treated patients, compared to a control group receiving etidronate and calcium Another study by van Cleemput et al found that 0.25-1 mcg/d of alfacalcidol PO begun approximately 2 weeks after cardiac transplantation improved but did not eliminate bone loss compared with oral etidronate.

De Sevaux and colleagues (2003) have examined vitamin D metabolites in a cohort of 61 renal transplant recipients over 2 years posttransplant. 1,25 –Dihydroxyvitamin D (1,25D) levels were low at transplantation in all patients and remained subnormal in 64% of patients at 3 months and 47% of patients at 6 months after transplant. After transplant, the intact PTH levels declined rapidly to just above the normal range. (From 3 months after transplant, the 1,25-D levels correlated with creatinine clearance.) The authors observed that nearly half of the patients demonstrated abnormal 1,25-D levels for at least 6 months after transplant, the period associated with the steepest decline in BMD.81

Renal transplant recipients receiving alfacalcidol (0.25 mcg/d) with calcium over 6 months had diminished bone loss at the LS and trochanter and almost complete prevention of bone loss at the femoral neck. Although there were unexpected differences in baseline BMD between the treated and untreated groups in this study, additional analysis of the data suggested that these differences could not explain the results. Severe hypercalcemia was slightly more common in the alfacalcidol group, although nearly all such patients had a high normal calcium at study entry. Urinary calcium was slightly higher also in the alfacalcidol group at 6 months after renal transplant.81

In addition, alphacalcidol may prevent fractures due to falls by improving muscle power.82

Calcitriol (1,25-dihydroxyvitamin D)

Kidney transplant and SPKT patients may continue to require posttransplant calcitriol for a brief period at doses lower than used during dialysis.83 However, therapy must be individualized because a significant proportion of patients have persistent hyperparathyroidism, and calcitriol could worsen hypercalciuria and hypercalcemia.

Studies of oral calcitriol in solid organ transplantation have yielded mixed results. Spinal bone loss was not prevented with low dose of calcitriol, 0.25 mcg/d or 0.5 mcg/48 h in heart and kidney recipients.59 In a single center in Spain, Toro et al described significant improvement at the femoral neck with alendronate and calcitriol administered late in the postoperative course. After approximately 13 months of treatment, a significant increase in BMD at the femoral neck was seen, although no improvement was seen at the level of the spine.

Begun immediately after heart or lung transplantation, 6 months of calcitriol at 0.5 mcg daily versus cyclic etidronate was associated with spine and femur neck bone loss, although less than in an untreated historical control group.84 This benefit clearly did not persist beyond 12–24 months.

In a randomized double blind 2-year study using higher doses of calcitriol at 0.5-0.75 mcg daily, beginning by 4 weeks posttransplantation, randomized to placebo or 12-24 months of calcitriol. Similar spine bone loss occurred in all groups, but less femur neck bone loss by one year with calcitriol. As in other studies, the benefit of calcitriol waned after its discontinuation.

As might be anticipated with this activated form of vitamin D, hypercalcemia and hypercalciuria were common, seen in 18% and 59% of patients treated with calcitriol. Routine monitoring of urine and serum calcium is indicated if calcitriol is prescribed.

Calcitriol, however, may have significant nonosteogenic benefits, which include recognized immunomodulatory and steroid-sparing actions. In a Turkish study of renal transplant recipients, patients who received calcitriol had lower PTH levels in the third year posttransplantation, as well as decreased requirements for pulse steroid doses. The increased creatinine levels were also lower in the calcitriol group. The authors concluded that calcitriol may reduce the rate of loss of renal function after renal transplant and protect renal allograft function.85

Vitamin D and calcium alone are clearly insufficient to prevent transplant-related bone loss.86 Bisphosphonates are clearly the drugs of choice for steroid-induced osteoporosis.75 Although the sun is the major source of vitamin D, unnecessary exposure to ultraviolet light cannot be recommended because of the increased incidence of skin cancers in transplant recipients.

Hypogonadism is common and frequently untreated in this medically complex population. Consider hormone replacement (estrogen or androgen) if evidence of hypogonadism exists, if not medically contraindicated.

Literature review of antiresorptive strategies in solid organ transplantation

  • Unfortunately, the literature regarding medical therapy to prevent or treat transplant-associated bone loss is plagued by relatively small numbers of patients with insufficient power to detect significant differences in BMD, differing immunosuppressant regimens, no randomization, or randomization at varying intervals following transplantation. This is particularly important since it is not appropriate to compare interventions in the early posttransplant period (within 6 mo of transplant) when bone loss is greatest, with later interventions. Moreover, the vast majority of studies are not powered to detect fracture outcomes.59
    • In humans, a pilot study in heart transplant recipients compared bisphosphonates administered (both PO and IV) with oral calcitriol against calcium and oral vitamin D. The antiresorptive group of 18 patients received 1 dose of intravenous pamidronate at 60 mg within 2 weeks of transplant and calcitriol at 0.25 mcg/d. This was followed by cyclical etidronate at 400 mg/d for 14 days every 3 months. A second group received similar calcium and vitamin D but no antiresorptives. After 12 months, spinal BMD was maintained in the group receiving bisphosphonates and calcitriol, whereas the comparator group lost 6-7%. Over this same period, femur-neck BMD fell 2.7% in the antiresorptive group, while the comparator group lost 10.6%.88
    • Valero et al (1995) studied 120 patients after liver transplantation. At 1-year posttransplant, 35% had documented osteoporosis. Patients received calcium at 1000 mg/d and cyclical etidronate 400 mg orally for 15 days every 3 months or calcitonin, 40 IU intramuscularly daily. After 1 year, this uncontrolled study showed significant improvements in vertebral BMD in both groups (6.4% and 8.2%, respectively).89
    • A controlled, nonrandomized, nonblinded study from the University of North Carolina examined the efficacy of intravenous pamidronate in 34 cystic fibrosis patients after lung transplantation. Pamidronate at 30 mg intravenously was administered every 3 months together with vitamin D at 800 IU/d and calcium at 1000 mg/d for 2 years. The pamidronate group was compared with a similar group receiving vitamin D and calcium alone. Although the study was not powered to detect differences in fracture prevalence, intravenous pamidronate was significantly more effective than placebo in improving BMD. Over the 2 years, patients gained approximately 8.8% BMD at the LS spine and 8.2% at the femur.90
    • The rapid early bone loss during the first 12 months following renal transplant can be prevented by intravenous pamidronate. In a prospective, randomized, controlled study, 26 male renal transplant patients received either placebo or intravenous pamidronate at 0.5 mg/kg at the time of transplant and 1 month later. All patients received prednisolone, cyclosporine, and azathioprine. Patient profiles were similar, as were PTH levels. With transplantation, similar decreases in serum creatinine levels were observed in both groups. At 12 months posttransplant, spine and femur-neck BMD were preserved in the pamidronate group, whereas in the control group, spine and femur-neck BMD fell 6.4% and 9%, respectively. In this small study, transient hypocalcemia was the only noted adverse effect, seen in 2 patients.91
    • Haas et al (2003) initially described the use of a third-generation bisphosphonate, zoledronic acid to prevent bone loss in the first 6 months postrenal transplant.92 In a randomized, placebo-controlled study sponsored by Novartis (manufacturer of Zoledronate), 20 renal transplant recipients received either 4 mg of zoledronic acid or placebo twice within 3 months posttransplant. Twenty-four of 28 subjects received Rocaltrol.
  • In addition to BMD by DEXA, mean trabecular calcium and trabecular morphometry were assessed by bone biopsy. Renal function did not change after zoledronic acid infusion. Two IV infusions of zoledronic acid prevented bone loss and increased average trabecular calcium concentration significantly over the first 6 months after transplant, compared with placebo group in which no change was seen.
  • BMD at the femoral neck showed no change in the zoledronic acid group but fell in the placebo group. BMD at the lumbar spine increased in the zoledronic acid group and was unchanged in the placebo group. Improved trabecular mineralization and architecture despite ongoing use of high-dose steroids was notable. Cancellous bone was stabilized. An increase in osteoid surface was seen and osteomalacia excluded based on bone turnover markers, although tetracycline labeling was not performed.
  • The increase in bone mineralization density distribution with zoledronate suggested increased trabecular mineralization and argued against osteomalacia. Adynamic bone disease was excluded on the basis of increased osteoid in the zoledronic acid group.
  • Disappointingly, the early bone sparing effects of short- term zoledronate conferred no sustained benefit compared with placebo at 3 years after transplantation.
    • A study of 40 patients examined the effects of oral alendronate, calcitriol, and calcium on bone loss at least 6 months following renal transplantation.83 The scores were depressed, suggesting at least osteopenia at all measured sites (ie, lumbar spine, -2.4 ±1; total femur, -2 ±0.7; femoral neck, -2.2 ±0.6).
      • During a 12-month period of observation, while subjects received 980 mg of dietary calcium, BMD fell further. Bone density decreased at the spine (-2.6 ± 5.7%, P <.01), total femur (-1.4 ± 4.2%, P <.05), and femoral neck (-2 ± 3%, P <.001).
      • Subjects were then randomized to alendronate plus calcitriol and calcium versus calcium and calcitriol alone. After 12 months of calcium 500 mg/d with 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.
    • Another study demonstrated that the rapid, severe bone loss associated with heart transplantation could be attenuated by either of two 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.93
    • 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 documented.57
    • 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.94 Similarly, a 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.95

      Another study looked at the results of bisphosphonate therapy administered to kidney transplant patients after the first posttransplant year. The study's patients, who were retrospectively assessed, underwent BMD measurements approximately 1 year after transplantation and again about 2.5 years after that, with 315 patients receiving bisphosphonate during that interval and 239 receiving no bisphosphonate. The authors found significant bone preservation in the femoral neck in the bisphosphonate group but nonetheless saw no correlation between bone loss at the femoral neck and fracture rates in the study's patients, whether or not they had undergone bisphosphonate therapy96 .
    • Transdermal estrogen therapy protects postmenopausal women with liver transplants from osteoporosis, similarly to healthy postmenopausal women.97 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.98
    • It is a National Kidney Foundation (K/DOQI) recommendation that if a BMD t-score is equal to or less than –2 at the time of transplantation or at subsequent evaluations, that therapy with parenteral amino bisphosphonate should be considered. There remain significant concerns for the use of bisphosphonates in renal patients with preexisting low bone turnover disease, wherein bisphosphonates could further slow bone turnover and potentially increase fracture rate.81

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. Adequate nutrition is essential for optimal bone health and essential for overall well-being in transplant recipients. A significant number of patients have compromised nutritional status after successful organ transplantation. Malnutrition has been associated with increased morbidity and higher rates of hospitalization. Low pretransplant body weight that remains low posttransplant negatively affects bone density. Renal transplant recipients with osteoporosis have lower posttransplant cholesterol and HDL levels (likely attributable to nutritional deficiencies).85 Global assessment of nutritional status by a certified dietician to detect malnutrition followed by appropriate nutritional interventions may be necessary in the transplant recipient.99

Activity

Exercise that provides a mechanical load to bone represents an osteogenic stimulus. In a 6-month, randomized, controlled clinical trial in heart transplant recipients, resistance exercise training in addition to alendronate reversed glucocorticoid-induced osteoporosis. Twenty-five heart transplant recipients were randomly assigned to alendronate 10 mg daily, alendronate plus specific resistance exercises, or a nonintervention control group. Resistance training included lumbar extension exercises performed 1 day per week and 8 variable resistance exercises performed twice per week.

Pretransplantation BMD did not differ between the 3 groups. The control group had ongoing significant losses of BMD after 3 and 6 months. Once alendronate was begun, no further regional loss of BMD was noted. Combined therapy of alendronate with resistance exercise was more efficacious than alendronate alone in restoring BMD in heart transplant recipients. This combination restored BMD of the whole body, femur neck, and lumbar vertebra to within 0.9%, 2.1%, and 3.4% of pretransplantation levels respectively.100

Similar exercise-associated preservation of bone mass was demonstrated in the same population in a recent prospective study of nasal calcitonin with and without resistance exercise in 18 heart transplant recipients. Lumbar BMD declined to 16.9% below pretransplant levels in the calcitonin only group, whereas the calcitonin plus exercise group achieved BMD results to within 5% of their pretransplant levels by 8 months after transplant.101

Regular weightbearing 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. Following transplantation, weightbearing exercise should be resumed as soon as possible, and a prescribed rehabilitation program encouraged.59

Medication

Any patient who meets World Health Organization (WHO) criteria for low bone mass (osteoporosis) should receive pharmacologic treatment similar to any other patient with osteoporosis or osteopenia. There are no specific FDA approved therapies for posttransplantation osteoporosis. Therapeutic strategies are extrapolated from nontransplant situations and based on relatively small numbers of patients in clinical trials (see Medical Care). 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.102

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.103  

Of particular concern in the renal transplant population, bisphosphonates are potentially nephrotoxic. Acute renal failure with acute tubular necrosis (ATN) in association with several bisphosphonates has been reported. In 2003, Banerjee described ATN following high-dose pamidronate, 60 mg for 3 doses over 2 weeks for hypercalcemia of unknown etiology,3 and in this same year, Chang et al described renal failure with the use of zoledronic acid.104  

Alendronate (Fosamax), ibandronate (Boniva), and risedronate (Actonel) are 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.105,106


Ibandronate (Boniva)

Inhibits osteoclast-mediated bone resorption. In postmenopausal women, it reduces bone turnover rate, leading to a net gain in bone mass.

Adult

2.5 mg PO qd; administer with water at least 1 h prior to first food or beverages (other than water) of the day
Alternatively, 150 mg PO once monthly on the same date each month or 3 mg IV push (infuse over 15-30 sec) q3mo

Pediatric

Not established

Multivalent cations (eg, calcium, aluminum, magnesium, iron) decrease absorption, administer ibandronate at least 1 h prior to vitamin and mineral supplements; NSAIDs may aggravate GI irritation

Documented hypersensitivity; uncorrected hypocalcemia; inability to stand or sit upright for at least 60 min following drug administration

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

May cause upper GI disorders (eg, dysphagia, esophagitis, ulceration), minimize GI risk by standing or sitting upright 1 h following dose; calcium and vitamin D supplementation required; not recommended with severe renal impairment (ie, CrCl <30 mL/min)


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

Prophylaxis: 5 mg PO qd
Treatment: 10 mg PO qd; alternatively, 70 mg PO qwk

Pediatric

Not established

Documented hypersensitivity; hypocalcemia, esophageal abnormalities, inability to stand upright for 30 min

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

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; osteonecrosis of the jaw associated with bisphosphonate derivative use


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

5 mg PO qd; alternatively, 35 mg PO qwk

Pediatric

Not established

Documented hypersensitivity, hypocalcemia, and renal impairment

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor 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; osteonecrosis of the jaw associated with bisphosphonate derivative use

Endocrine agents

These agents may inhibit osteoclastic bone resorption.


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

200 U intranasally into one nostril qd; alternate nostrils qd

Pediatric

Not established

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Hypocalcemia may occur; examine urine sediment during prolonged therapy


Teriparatide (Forteo)

Recombinant human parathyroid hormone rhPTH(1-34), which has identical sequence to 34 N-terminal amino acids (biologically active region) of 84-amino acid human parathyroid hormone (PTH). Acts as endogenous PTH, thus regulating calcium and phosphate metabolism in bone and kidney. Works primarily to stimulate new bone by increasing number and activity of osteoblasts (bone-forming cells). Additional physiological actions include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption.
When administered with calcium and vitamin D, teriparatide increases bone mineral density and decreases risk of fractures in patients with osteoporosis.

Adult

20 mcg SC qd

Pediatric

Not established

Documented hypersensitivity; increased risk for osteosarcoma (including those with Paget disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses, or prior radiation therapy involving the skeleton); children or growing adults; patients with bone metastases or history of skeletal malignancies, and those with metabolic bone diseases other than osteoporosis

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Monitor for hypercalcemia; may cause orthostatic hypotension (particularly following first several doses), dizziness, or leg cramps

More on Osteoporosis in Solid Organ Transplantation

Overview: Osteoporosis in Solid Organ Transplantation
Differential Diagnoses & Workup: Osteoporosis in Solid Organ Transplantation
Treatment & Medication: Osteoporosis in Solid Organ Transplantation
Follow-up: Osteoporosis in Solid Organ Transplantation
Multimedia: Osteoporosis in Solid Organ Transplantation
References
Further Reading
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Further Reading

Related eMedicine topics:
Fracture, Cervical Spine
Heart Transplantation [Pediatrics: Surgery]
Heart Transplantation [Transplantation]
Immunosuppression [Pediatrics: Surgery]
Immunosuppression [Transplantation]
Kidney Transplantation
Liver Transplantation [Pediatrics: Surgery]
Liver Transplantation [Transplantation]
Lower Cervical Spine Fractures and Dislocations
Lumbar Compression Fracture
Lumbar Spine Fractures and Dislocations
Lung Transplantation [Pediatrics: Surgery]
Lung Transplantation [Transplantation]
Osteoporosis [Orthopedic Surgery]
Osteoporosis [Pediatrics: General Medicine]
Osteoporosis, Involutional
Osteoporosis (Primary)
Osteoporosis (Secondary)
Pancreas Transplantation
Renal Transplantation (Medical)
Renal Transplantation (Urology)
Transplants, Heart
Transplants, Liver
Transplants, Lung
Transplants, Renal
Vertebral Fracture

Clinical guidelines:
AASLD practice guidelines: evaluation of the patient for liver transplantation. American Association for the Study of Liver Diseases - Private Nonprofit Research Organization.  2000 Jan (revised 2005 Jun).  26 pages.  NGC:004333

Clinical trials:
Effects of Zoledronic Acid Versu Alendronate on Bone Loss After Kidney and Kidney/Pancreas Transplants

Ibandronate Versus Placebo in the Prevention of Bone Loss After Renal Transplantation

Vitamin D3 Substitution in Vitamin D Deficient Kidney Transplant Recipients (VITA-D)

Zoledronic Acid Versus Alendronate for Prevention of Bone Loss After Organ Transplantation (CTX)

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Keywords

osteoporosis, transplantation, transplant, transplants, osteopenia, kidney transplant, liver transplant, heart transplant, lung transplant, organ transplant, bone density, bone loss, bone mineral density, organ transplantation, immunosuppressive, immunosuppressant, liver transplantation, heart transplantation, lung transplantation, kidney transplantation, kidney/pancreas transplantation

simultaneous pancreas-kidney transplantation, SPKT, low bone mass, glucocorticoid-induced osteoporosis, low body weight, estrogen deficiency, androgen deficiency, calcium deficiency, vitamin D deficiency, thyroid hormone excess, vertebral fractures, hip fractures, negative calcium balance, bone loss, osteoporotic fractures, fragility fractures, cystic fibrosis, primary biliary cirrhosis, PBC, osteogenesis imperfecta

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Contributor Information and Disclosures

Author

Carmel M Fratianni, MD, FACE, Associate Professor of Clinical Medicine, Department of Internal Medicine, Division of Endocrinology, Metabolism and Molecular Medicine, Southern Illinois University School of Medicine
Carmel M Fratianni, MD, FACE is a member of the following medical societies: American Association of Clinical Endocrinologists, American College of Endocrinology, American Diabetes Association, American Thyroid Association, Endocrine Society, and Illinois State Medical Society
Disclosure: Nothing to disclose.

Medical Editor

Steven R Gambert, MD, MACP, Chairman, Department of Medicine, Physician-in-Chief, Sinai Hospital of Baltimore; Professor of Medicine, Program Director, Internal Medicine Program, Johns Hopkins University School of Medicine
Steven R Gambert, MD, MACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physician Executives, American College of Physicians, American Geriatrics Society, Association of Professors of Medicine, Endocrine Society, and Gerontological Society of America
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Don S Schalch, MD, Professor Emeritus, Department of Internal Medicine, Division of Endocrinology, University of Wisconsin Hospitals and Clinics
Don S Schalch, MD is a member of the following medical societies: American Diabetes Association, American Federation for Medical Research, Central Society for Clinical Research, and Endocrine Society
Disclosure: Nothing to disclose.

CME Editor

Mark Cooper, MBBS, PhD, FRACP, Head, Diabetes & Metabolism Division, Baker Heart Research Institute, Professor of Medicine, Monash University
Disclosure: Nothing to disclose.

Chief Editor

George T Griffing, MD, Professor of Medicine, St Louis University School of Medicine
George T Griffing, MD is a member of the following medical societies: American Association for the Advancement of Science, American College of Medical Practice Executives, American College of Physician Executives, American College of Physicians, American Diabetes Association, American Federation for Medical Research, American Heart Association, Central Society for Clinical Research, Endocrine Society, International Society for Clinical Densitometry, and Southern Society for Clinical Investigation
Disclosure: Nothing to disclose.

 
 
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