Chapter 25. Drugs That Affect Bone Mineral Homeostasis

Calcium and phosphate are the major mineral constituents of bone and are also two of the most important minerals for general cellular function. Accordingly, the body has evolved a complex set of mechanisms by which calcium and phosphate homeostasis is carefully maintained. Approximately 98% of the 1 to 2 kg of calcium and 85% of the 1 kg of phosphorus in the human adult are found in bone, the principal reservoir for these minerals. Mineral homeostasis is dynamic, with constant remodeling of bone and ready exchange of bone minerals with free ions in the extracellular fluid. Bone also serves as the principal structural support for the body and provides space for hematopoiesis in the bone marrow. Abnormalities in bone mineral homeostasis can underlie electrolyte disturbances, resulting in the clinical manifestations of muscle weakness, tetany, and coma. Dysfunction in bone mineral homeostasis can also disturb the structural support of the body in the form of osteoporosis and fractures. Hematopoietic capacity may also be reduced in conditions such as infantile osteopetrosis.

The average American diet provides 600 to 1000 mg of calcium per day, of which a net amount of approximately 100 to 250 mg is absorbed. Absorption principally occurs in the duodenum and upper jejunum, whereas secretion principally occurs in the ileum. The amount of phosphorus in the American diet is about the same as that of calcium. However, the efficiency of phosphate absorption, which mostly occurs in the jejunum, is greater, ranging from 70 to 90%, depending on intake. The movement of calcium and phosphate across the intestinal and renal epithelia is closely regulated. At steady state, renal excretion of calcium and phosphate balances intestinal absorption. Most of the time, over 98% of filtered calcium and 85% of filtered phosphate is reabsorbed by the kidneys.

The drugs that are used clinically to modulate bone homeostasis can be divided into endogenous molecules and exogenous substances (Figure 25–1).

Endogenous Substances

The two hormones that serve as the principal regulators of calcium and phosphate homeostasis are parathyroid hormone (PTH), a protein, and biologically active metabolites of the steroid vitamin D (Figure 25–2). Other hormones such as calcitonin, prolactin, growth hormone, insulin, thyroid hormone, glucocorticoids, and gonadal steroids serve secondary roles in calcium and phosphate homeostasis. Several of these hormones, such as calcitonin, glucocorticoids, and estrogens, have efficacy in the treatment of bone mineral disorders. In addition, calcium, phosphate, and other ions such as sodium alter calcium and phosphate homeostasis.

Vitamin D

Vitamin D, a derivative of 7-dehydrocholesterol, is formed in the skin under the influence of ultraviolet light. Vitamin D is also found in some foods and is a nutritional additive in milk and in calcium supplements. Active metabolites of vitamin D are formed in the liver (25-hydroxyvitamin D, or calcifediol) and the kidney (1,25-dihydroxyvitamin D [1,25[OH]2D3], or calcitriol, plus other metabolites). Because it is a fat-soluble vitamin, excess vitamin D is stored in adipose tissue. The metabolites of vitamin D differ in the number of hydroxyl groups attached to the steroid ring (Table 25–1). The actions of these metabolites include increased intestinal calcium and phosphorus absorption, decreased renal excretion of minerals, and a net increase in blood levels of both calcium and phosphorus (Figure 25–2, Table 25–2). These actions are mediated by activation of one or possibly a family of nuclear receptors that regulate gene expression. Of the vitamin D metabolites, 1,25[OH]2D is the most potent in stimulating intestinal calcium and phosphate absorption and bone resorption. In contrast, bone formation can be increased by the administration of a different metabolite, 24,25-dihydroxyvitamin D (secalcifediol, 24,25(OH)2D3 ). Vitamin D supplements and synthetic derivatives are used in the treatment of deficiency states, such as nephrotic syndrome and nutritional rickets. They are also used, in combination with calcium supplementation and other drugs, in the prevention and treatment of osteoporosis in older women and men. Moreover, a number of calcitriol analogs are being synthesized in an effort to examine their clinical usefulness in a variety of nonclassic conditions. For example, calcipotriene (calcipotriol) is currently used to treat psoriasis, a hyperproliferative skin disorder. Doxercalciferol and paricalcitol have recently been approved for treating secondary hyperparathyroidism in patients with renal failure.

Parathyroid Hormone

By regulating calcium and phosphate flux across cellular membranes in bone and kidney, PTH increases serum calcium while decreasing serum phosphate (Figure 25–2, Table 25–2). By an indirect mechanism, PTH increases the activity and number of osteoclasts, cells responsible for bone resorption. PTH activates G protein–coupled receptors on bone–forming osteoblasts, inducing a membrane-bound protein called RANK ligand. RANK ligand increases both the number and activity of osteoclasts. Thus, bone remodeling is actually initiated by osteoclastic bone resorption and followed by osteoblastic bone formation. Although PTH enhances both bone resorption and bone formation, the net effect of excess PTH is increased bone resorption. However, when administered in low, intermittent doses, PTH increases bone formation without stimulating bone resorption. Based on this effect, recombinant PTH 1-34 (teriparatide) has been approved by the United States Food and Drug Administration (FDA) for the treatment of osteoporosis in postmenopausal women. In the kidney, PTH increases calcium and magnesium resorption while reducing the resorption of phosphate, amino acids, bicarbonate, sodium, chloride, and sulfate. Another important action of PTH in the kidney is its stimulation of calcitriol production.

Interaction of PTH and Vitamin D Metabolites

A summary of the principal actions of PTH and vitamin D on intestine, kidney, and bone is presented in Table 25–2. The net effect of PTH is to raise serum calcium and reduce serum phosphate; the net effect of vitamin D is to raise serum levels of both. Regulation of calcium and phosphate homeostasis is achieved through a variety of feedback loops. In the parathyroid gland, specialized G protein–coupled receptors sense extracellular calcium concentration and couple this with intracellular calcium concentration. For example, when extracellular calcium falls, intracellular calcium falls in parallel and parathyroid cells secrete more PTH. Conversely, a rise in intracellular calcium concentration in parathyroid cells inhibits PTH secretion. Phosphate ion indirectly stimulates PTH secretion by forming complexes with calcium in the serum. These complexes decrease the concentration of ionized calcium, which is the form of calcium that binds to the calcium-sensing receptor. In the kidney, high levels of calcium and phosphate reduce calcitriol production and increase secalcifediolproduction. Since calcitriol is far more potent than secalcifediol at increasing serum calcium and phosphate, the net effect of calcitriol’s action is feedback inhibition of vitamin D’s main action. Calcitriol inhibits PTH secretion through a direct action on PTH gene transcription. This provides yet another negative feedback loop because PTH is a major stimulus for calcitriol production. The ability of calcitriol to inhibit PTH secretion directly can be exploited by administering analogs that have less effect on serum calcium. Such drugs are proving useful in the management of the secondary hyperparathyroidism that accompanies renal failure, and may be useful in selected cases of primary hyperparathyroidism.

Calcitonin

Calcitonin is a peptide hormone secreted by the parafollicular cells of the thyroid gland. The principal effect of calcitonin is to lower serum calcium and phosphate by actions on bone and kidney (Figure 25–2). Calcitonin inhibits osteoclastic bone resorption. During the initial stages of exogenous calcitonin administration, bone formation is not impaired. However, with continued use, both formation and resorption of bone are reduced. In the kidney, calcitonin reduces resorption of a number of ions including calcium, phosphate, sodium, potassium, and magnesium. Tissues other than bone and kidney are also affected by calcitonin.

In pharmacologic dosages, calcitonin reduces gastric acid output by inhibiting gastrin secretion, and increases secretion of sodium, potassium, chloride, and water into the gut. Although calcitonin does not significantly increase bone mass, it reduces the rate of bone loss, making it a useful drug for the treatment of osteoporosis. Its ability to block bone resorption and lower serum calcium also make it useful for treating Paget’s disease and hypercalcemia. Calcitonin is administered by injection or nasal spray.

Estrogens

These compounds were previously discussed (Chapter 22) in relation to their regulation of sexual development, metabolic activity, and reproduction. Estrogens and selective estrogen receptor modulators (SERMs) such as tamoxifen or raloxifene prevent or delay bone loss in postmenopausal women. However, long-term estrogen treatment increases cardiovascular and cancer risks. Although it is not as effective as estrogen at increasing bone density, raloxifene reduces bone fractures and may reduce the risk of breast cancer.

Glucocorticoids

The glucocorticoids have multiple influences on metabolism that inhibit bone mineral maintenance (Chapter 23). Glucocorticoids alter bone mineral homeostasis by antagonizing vitamin D–stimulated intestinal calcium transport, stimulating renal calcium excretion, and blocking bone formation. As a result, chronic systemic use of glucocorticoids is a common cause of osteoporosis in adults and stunted skeletal development in children. However, glucocorticoids are useful in the intermediate-term treatment of hypercalcemia associated with lymphomas and granulomatous diseases such as sarcoidosis.

Exogenous Agents

A variety of other types of drugs are used to regulate bone mineral homeostasis. The bisphosphonates were developed for that purpose. The antibiotic plicamycin and the thiazide diuretics were developed for other clinical uses, but have found clinical value in treating disorders of bone mineral homeostasis.

Bisphosphonates

The bisphosphonates (alendronate, etidronate, ibandronate, pamidronate, risedronate, tiludronate, zoledronate) are short-chain organic polyphosphate compounds that reduce both resorption and formation of bone by acting on the basic hydroxyapatite crystal structure of bone. The bisphosphonates have other complex cellular effects, including inhibiting vitamin D production, inhibiting calcium absorption from the gastrointestinal tract, and directly inhibiting osteoclast function. In postmenopausal women, chronic bisphosphonate therapy slows osteoporosis progression and reduces fractures. The older drugs (etidronate, pamidronate) cause bone mineralization defects and lose their effectiveness over a 12-month period. Alendronate and risedronate cause fewer bone problems and are effective for at least 5 years. These two drugs are commonly used for treating postmenopausal and glucocorticoid-induced osteoporosis and for Paget’s disease. Alendronate, used in combination with hormone replacement therapy, further increases bone mass in postmenopausal patients.

Oral bioavailability of bisphosphonates is low (<10%), and food impairs their absorption. Esophageal ulceration may also occur. Patients should take these drugs with large quantities of water, remain upright for 30 minutes, and avoid situations that permit esophageal reflux (i.e., activities that increase intra-abdominal pressure). In the prevention or treatment of osteoporosis, once-weekly administration of a relatively large dose of a bisphosphonate is as efficacious as daily administration of a smaller dose and does not result in more toxicity. Annual intravenous administration of zoledronate has similarly been found to be effective.

Fluoride

Appropriate concentrations of fluoride ion in drinking water (0.5 to 1.0 ppm) or as an additive in toothpaste have a well-documented ability to reduce dental caries. Chronic exposure to fluoride ion, especially in high concentrations, may increase new bone synthesis. What is not clear, however, is whether this new bone has normal strength. Clinical trials of fluoride in patients with osteoporosis have not demonstrated a reduced incidence of fractures. Acute fluoride toxicity, usually caused by ingestion of rat poison, is manifested by gastrointestinal and neurologic symptoms. Chronic toxicity (fluorosis) includes ectopic bone formation (exostoses) and calcified bumps on bones.

Thiazide Diuretics

This drug class was previously discussed in relation to the treatment of hypertension (Chapter 7). Thiazides increase the effectiveness of parathyroid hormone in stimulating renal reabsorption of calcium. In the distal tubule, thiazides block sodium reabsorption at the luminal surface. The resultant fall in intracellular sodium causes a greater calcium-sodium exchange at basolateral membranes, bringing sodium into distal tubule cells and transporting calcium out into the interstitial space. The net effect of thiazide diuretics is enhanced renal calcium reabsorption. Thiazides are useful in reducing hypercalciuria and nephrolithiasis in subjects with idiopathic hypercalciuria. They are not used to treat osteoporosis.

Plicamycin (Mithramycin)

This antibiotic is used to reduce serum calcium and bone resorption in Paget’s disease and hypercalcemia. Because of the risk of complications, such as thrombocytopenia, hemorrhage, and hepatic and renal damage, plicamycin is not commonly prescribed. The drug is mainly restricted to short-term treatment of serious hypercalcemia.

Osteoporosis

Osteoporosis is an abnormal loss of bone that predisposes an individual to fractures. Compact bone is affected more than trabecular bone. Osteoporosis is most common in postmenopausal women and elderly men. Osteoporosis can result from chronic administration of glucocorticoids or other drugs, endocrine diseases such as thyrotoxicosis or hyperparathyroidism, malabsorption syndrome, alcohol abuse and cigarette smoking, and idiopathic conditions.

The ability of some agents to reverse the bone loss of osteoporosis is shown in Figure 25–3. The postmenopausal form of osteoporosis may be accompanied by lower calcitriol levels and reduced intestinal calcium transport. This form of osteoporosis is secondary to the reduced estrogen production that accompanies menopause; it can be treated with estrogen. However, concerns about increases in breast and endometrial cancer risk and cardiovascular adverse effects have dramatically reduced enthusiasm for this form of therapy. The selective estrogen receptor modulator (SERM) raloxifene (Chapter 22) avoids the increased risk of breast and uterine cancer associated with estrogen supplementation while maintaining the benefit to bone. Raloxifene appears to protect against spine fractures, but not hip fractures. In contrast, bisphosphonates and teriparatide protect against both fracture types. Raloxifene does not prevent hot flushes and imposes the same increased risk of venous thrombosis as estrogen.

To counter the reduced intestinal calcium transport associated with osteoporosis, vitamin D therapy is sometimes employed along with dietary calcium supplementation, but there is little evidence that pharmacologic doses of vitamin D are of much additional benefit beyond cyclic estrogens and calcium supplementation. However, in several large studies, vitamin D supplementation (400 to 800 IU/day) and calcitriol and its analog 1α(OH)D3 have been shown to increase bone mass and, in several recent studies, to reduce fractures. Use of these agents for osteoporosis is not approved by the FDA.

Calcitonin is approved for the treatment of postmenopausal osteoporosis. It has been shown to increase bone mass and reduce fractures, but only in the spine.

Bisphosphonates are efficacious inhibitors of bone resorption. They increase bone density and reduce the risk of fractures in the hip, spine, and other locations. Alendronate, risedronate, and zoledronate are approved for osteoporosis treatment. These drugs are effective in treating osteoporosis of various causes in men as well as women.

Despite early promise that fluoride might be useful in the prevention or treatment of postmenopausal osteoporosis, this form of therapy remains controversial. A new formulation of fluoride (slow release of a lower dose) appears to avoid much of the toxicity of earlier formulations and may reduce fracture rates. This formulation is under consideration for approval by the FDA.

Teriparatide, the recombinant form of PTH 1–34, has recently been approved for treatment of osteoporosis. Teriparatide is given subcutaneously in a dosage of 20 mcg daily. Like fluoride, teriparatide stimulates new bone formation. However, in contrast to fluoride, teriparatide-stimulated new bone appears structurally normal and is associated with a substantial reduction in the incidence of fractures.

Chronic Renal Failure

The major problems of chronic renal failure that impact bone mineral homeostasis are reduction of calcitriol and secalcifediol production, retention of phosphate (with associated reduction in ionized calcium levels), and secondary hyperparathyroidism. With reduced calcitriol production, less calcium is absorbed from the intestine and less bone is resorbed. The most common clinical presentation is hypocalcemia and hyperphosphatemia. The resulting hypocalcemia usually furthers the hyperparathyroidism. The skeletal system shows a mixture of osteomalacia, abnormal bone formation due to inadequate mineralization, and osteitis fibrosa, excessive bone resorption with fibrotic replacement of resorption cavities. Some patients may become hypercalcemic. The most common cause of the hypercalcemia is severe secondary hyperparathyroidism. Vitamin D supplementation is often prescribed for dialysis patients in chronic renal failure. The choice of supplement depends upon the type and extent of bone disease and hyperparathyroidism. Regardless of the drug employed, careful attention to serum calcium and phosphate levels is required. Calcium supplements and phosphate restriction are combined with vitamin D metabolites. Serum PTH levels are monitored to determine whether therapy is correcting or preventing secondary hyperparathyroidism. Vitamin D metabolites are monitored to assess compliance, absorption, and metabolism.

Other Clinical Disorders

Other clinical disorders involving bone mineralization include nutritional rickets, which can be corrected with vitamin D supplementation or exposure to sunlight. A number of disorders involving the gastrointestinal system, such as biliary cirrhosis, may result in abnormal calcium and phosphate homeostasis that ultimately leads to bone disease. This bone involvement may be the result of abnormal calcium or vitamin D intestinal absorption, or systemic toxins from cholestasis that inhibit osteoblast function. Clinically, the bone disease secondary to gastrointestinal dysfunction manifests as osteoporosis and osteomalacia, but without osteitis fibrosa. Treatment includes supplementation with vitamin D or its analogs and dietary calcium supplementation.

Patients with nephrotic syndrome lose vitamin D metabolites in the urine and subsequently may develop bone disease. Treatment includes vitamin D.

Paget’s disease is a localized bone disease characterized by uncontrolled osteoclastic bone resorption with secondary increases in bone formation. The goal of treatment is to reduce bone pain and stabilize or prevent other problems such as progressive deformity, hearing loss, high-output cardiac failure, and immobilization hypercalcemia. Calcitonin and bisphosphonates are first-line agents for treatment of Paget’s disease. Patients who fail to respond to these drugs may respond to plicamycin.

Physical therapists develop exercise programs, which when combined with pharmacotherapy and diet, may delay osteoporosis. Therapists also see patients with osteoporosis for treatment of pain and dysfunction resulting from osteoporosis-induced fractures.

Multiple exercise formats can delay osteoporosis. Weight-bearing exercises (e.g., walking, stair climbing), resistive exercises (e.g., weight lifting, swimming), and aerobic exercises have been shown to delay bone loss and osteoporosis. Of these, resistive training may provide the strongest stimulus for bone remodeling and reduced bone loss. In contrast to pharmacotherapy and diet modification, exercise can reduce the occurrence of comorbidities associated with osteoporosis (such as diabetes mellitus), and maintain and improve cardiovascular and respiratory status. Exercise can also improve strength and balance, which have the added benefit of preventing falls and associated fractures. Finally, exercise may enhance pharmacologically increased bone formation, suggesting that the combination of exercise and drug therapy may optimize building bone mass.

Adverse Drug Reactions

• • Bisphosphonates may cause esophageal ulceration.
• • Calcitonin administration may cause gastrointestinal distress.
• • SERMs such as raloxifene may cause hot flushes and nausea.
• • Teriparatide administration may cause chest pain and dyspnea, dizziness, and gastrointestinal distress.

Effects Interfering with Rehabilitation

• • Patients taking bisphosphonates within 30 minutes prior to therapy may experience esophageal pain if they are horizontal during the treatment session.
• • Therapy sessions may exacerbate gastrointestinal distress due to calcitonin administration.
• • Therapy sessions may exacerbate gastrointestinal distress or hot flushes of SERM medications such as raloxifene.
• • Therapy sessions may exacerbate adverse effects of teriparatide administration.

Possible Therapy Solutions

• • Have patients take bisphosphonates after or at least 1 hour prior to therapy sessions.
• • Have patients take calcitonin on a day when therapy is not scheduled.
• • Schedule therapy sessions for days when SERMdrugs or teriparatide are not administered, or on a day prior to drug administration.

Potentiation of Functional Outcomes Secondary to Drug Therapy

• • In postmenopausal women with osteoporosis, exercise without estrogen replacement therapy is effective in increasing or maintaining bone mineral density at certain sites.
• • Pharmacotherapy and exercise programs individually, and in combination, help to prevent osteoporosis.

Brief History: The patient is a 55-year-old disabled male with a 20-year history of rheumatoid arthritis (RA) and a body mass index of 27. He has bilateral knee joint replacements, the most recent performed 2 years ago. The patient ambulates with two single-point canes to increase mobility and decrease knee pain. He is not currently involved in a regular conditioning program. Three weeks ago, the patient was diagnosed with locally invasive prostate cancer. In conjunction with beginning pharmacotherapy for prostate cancer, the patient received a bone density study, which revealed osteoporosis. Owing to the results of the bone densitometry, the oncologist referred the patient to rehabilitation for development of a conditioning program.

Current Medical Status and Drug Therapy: Previous and current pharmacotherapy for RA included intermittent use of anti-inflammatory glucocorticoids (Chapter 23) and regular medication with nonsteroidal anti-inflammatory drugs and disease-modifying antirheumatic drugs (Chapter 34). The pharmacotherapy for prostate cancer is designed to suppress testosterone production and destroy the in situ cancer cells. Suppression of endogenous testosterone production will be accomplished by continuous dosing with goserelin plus flutamide for the first several weeks to prevent flare-up (Chapter 22). Radiation therapy will be initiated to destroy in situ cancer cells in the prostate. To help prevent further bone loss, over-the-counter vitamin D and calcium carbonate and the prescription drug alendronate will be given with initiation of the cancer pharmacotherapy. These are to be continued as long as goserelin is administered.

Rehabilitation Setting: The patient ambulates independently into the clinic with both canes. He states that recurring acute painful RA flare-ups prevent him from aerobic activities. The near constant knee pain limits him to household and limited community ambulation. His upper body function usually does not limit his activities; however, this is also limited during acute RA flare-ups. After evaluation, the physical therapist recommends a conditioning program that includes upper extremity resistive exercises, as pain and acute episodes of RA allow. Since ambulation or resistive exercises including the lower extremities were limited by pain, the therapist develops an aquatherapy program. Aquatherapy includes ambulation on the clinic’s underwater treadmill at a water level that the patient finds comfortable. The program is developed at the clinic, and will be continued at the local recreation center where the patient can walk at a comfortable speed in the shallow end of the pool. The patient will return once every-other-week for treatment modification. The therapist encourages the patient to attempt swimming when he feels more comfortable in the water.

Problem/Clinical Options: In recognition of the patient’s current low bone mineral density, which probably stems from his intermittent glucocorticoid use and minimal physical activity, the oncologist made the referral for the development of a conditioning program. In addition, the antiandrogen pharmacotherapy for prostate cancer will suppress bone mineralization, further increasing the potential for osteoporosis. The purpose of the vitamin D, calcium, and alendronate is to minimize any further bone mineralization loss. An appropriate conditioning program in conjunction with anti-osteoporosis drugs will help minimize further bone loss, and may increase bone mineralization. Although aquatic activity is not as effective as resistive exercises in preventing bone demineralization in the lower extremities, the patient’s current limitations preclude resistive exercises. Aquatic therapy has the added benefits of maintaining cardiovascular and respiratory functions.

Vitamin D, Metabolites, and Analogs

Calcifediol (Calderol)

Oral: 20-, 50-mcg capsules

Calcitriol

Oral (Rocaltrol): 0.25-, 0.5-mcg capsules, 1 mcg/mL solution

Parenteral (Calcijex): 1 mcg/mL for injection

Cholecalciferol (D3) (Vitamin D3, Delta-D)

Oral: 400, 1000 IU tablets

Dihydrotachysterol (DHT) (DHT, Hytakerol)

Oral: 0.125-mg tablets, capsules; 0.2-, 0.4-mg tablets; 0.2 mg/mL intensol solution

Doxercalciferol (Hectoral)

Oral: 2.5-mcg capsules

Ergocalciferol (D2) (Vitamin D2, Calciferol, Drisdol)

Oral: 50,000 IU capsules; 8000 IU/mL drops

Parenteral: 500,000 IU/mL for injection

Paricalcitol (Zemplar)

Parenteral: 5 mcg/mL for injection

Calcium

Calcium Acetate (25% Calcium) (Phoslo)

Oral: 668-mg (167-mg calcium) tablets; 333.5-mg (84.5-mg calcium), 667-mg (169-mg calcium) capsules

Calcium Carbonate (40% Calcium) (Generic, Tums, Cal-Sup, Os-Cal 500, Others)

Oral: Numerous forms available containing 260–600 mg calcium per unit

Calcium Chloride (27% Calcium) (Generic)

Parenteral: 10% solution for IV injection only

Calcium Citrate (21% Calcium) (Generic, Citracal)

Oral: 950-mg (200-mg calcium), 2376-mg (500-mg calcium)

Calcium Glubionate (6.5% Calcium) (Calcionate, Calciquid)

Oral: 1.8 g (115-mg calcium)/5 mL syrup

Calcium Gluceptate (8% Calcium) (Calcium Gluceptate)

Parenteral: 1.1 g/5 mL solution for IM or IV injection

Calcium Gluconate (9% Calcium) (Generic)

Oral: 500-mg (45-mg calcium), 650-mg (58.5-mg calcium), 975-mg (87.75-mg calcium), 1-g (90-mg calcium) tablets

Parenteral: 10% solution for IV or IM injection

Calcium Lactate (13% Calcium) (Generic)

Oral: 650-mg (84.5-mg calcium), 770-mg (100-mg calcium) tablets

Tricalcium Phosphate (39% Calcium) (Posture)

Oral: 1565-mg (600-mg calcium) tablets (as phosphate)

Phosphate and Phosphate Binder

Phosphate

Oral (Fleet Phospho-soda): solution containing 2.5 g phosphate/5 mL (816 mg phosphorus/5 mL; 751 mg sodium/5 mL)

Oral (K-Phos-Neutral): tablets containing 250 mg phosphorus, 298 mg sodium

Oral (Neutra-Phos): For reconstitution in 75 mL water, packet containing 250 mg phosphorus; 164 mg sodium; 278 mg potassium

Oral (Neutra-Phos-K): For reconstitution in 75 mL water, packet containing 250 mg phosphorus; 556 mg potassium; 0 mg sodium

Parenteral (potassium or sodium phosphate): 3 mmol/mL

Sevelamer (Renagel)

Oral: 403-mg capsules

Other Drugs

Alendronate (Fosamax)

Oral: 5-, 10-, 35-, 40-, 70-mg tablets

Calcitonin-Salmon

Nasal spray (Miacalcin): 200 IU/puff

Parenteral (Calcimar, Miacalcin, Salmonine): 200 IU/mL for injection

Etidronate (Didronel)

Oral: 200-, 400-mg tablets

Parenteral: 300-mg/6 mL for IV injection

Pamidronate (Generic, Aredia)

Parenteral: 30, 60, 90 mg/vial

Plicamycin (Mithramycin) (Mithracin)

Parenteral: 2.5 mg per vial powder to reconstitute for injection

Risedronate (Actonel)

Oral: 5-, 30-, 35-mg tablets

Sodium Fluoride (Generic)

Oral: 0.55-mg (0.25-mg F), 1.1-mg (0.5 mg F), 2.2-mg (1-mg F) tablets; drops

Teriparatide (Forteo)

Subcutaneous: 250 mcg/mL from prefilled pen (3 mL)

Tiludronate (Skelid)

Oral: 200-mg tablets

Zoledronic Acid (Zometa)

Parenteral: 4 mg/vial