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CLINICAL USES OF PARATHYROID HORMONE, CALCITONIN, VITAMIN D, AND BISPHOSPHONATES
These hormones and drugs are used most commonly for disorders of calcium and bone metabolism rather than to correct specific hormone deficiencies. For example, the use of PTH replacement in hypoparathyroidism in the past was not practical because of the difficulty in obtaining purified hormone and the fact that it is injected subcutaneously. With the recent ability to produce large quantities of recombinant PTH (rPTH), its use will be more common, especially for severe osteoporosis.
Hypercalcemia is a common clinical condition that can accompany a variety of other medical conditions, such as sarcoidosis, vitamin D toxicity, hyperparathyroidism, and malignancy. When calcium levels are exceptionally high, adjunctive measures for the control of plasma cal-cium levels are necessary, as this is a medical emergency. Various modalities in combination are used to treat this condition; intravenous hydration with normal saline and the use of loop diuretics (e.g., furosemide) to induce calcium diuresis are the most important supportive measures.
The bisphosphonates are the most effective com-pounds available to treat hypercalcemia of malignancy. Pamidronate (Aredia) and zoledronic acid (Zometa) can be infused intravenously and are the most effective compounds available for rapid reduction of serum cal-cium levels.
Calcitonin is also effective in reducing serum cal-cium levels in life-threatening hypercalcemia; however, it is not as rapid or as effective as the bisphosphonates. Subcutaneous administration of salmon (Calcimar) or human (Cibacalcin) calcitonin reduces serum calcium levels within 3 to 5 days in 75 to 90% of malignant hy-percalcemias.
Plicamycin (Mithracin), an inhibitor of RNA synthe-sis in osteoclasts, reduces serum calcium levels when in-fused over 4 to 6 hours every 3 to 4 days. Plicamycin’s effects are slower than those of the bisphosphonates; the drug is a bone marrow suppressant that can compli-cate clinical management if the patient is already re-ceiving chemotherapy for the malignancy.
Postmenopausal osteoporosis is the most common form of osteoporosis. In perimenopausal women, the greatest amount of bone density is lost during the first 5 years after onset of menopause. Women going through meno-pause at a particularly early age are especially at risk for developing osteoporosis, and they should take some prophylactic regimen at the onset of menopause. Previously, estrogen replacement therapy (ERT), along with calcium supplementation and D3, were the stan-dard of care. However, the benefits of ERT, including increased bone density, decreased risk of colon cancer, and decreased vaginal atrophy, must be weighed against the slightly increased risk of breast cancer, endometrial cancer, stroke, and deep vein thrombosis. While unop-posed estrogen may slightly increase the incidence of endometrial cancer, appropriate combinations with a progestin negate such risk. Other compounds are avail-able for the prevention of osteoporosis. These include the selective estrogen receptor modulators, the bisphosphonates, and nasally administered calcitonin. For example, the bisphosphonates are now indicated for prophylaxis of osteoporosis when individ-uals are going to be treated with glucocorticoids or the gonadotropin antagonists.
Once bone loss is sufficient to result in a compression fracture, pharmacological therapy is much less effective. However, even after fractures have occurred, the use of the bisphosphonates and rPTH has been shown to in-crease bone densities and reduce the rate of subsequent fractures. Nasal calcitonin (200 units daily) is effective in promoting fracture healing and also exhibits an anal-gesic effect by reducing pain in persons with acute lum-bar compression fractures. Whatever compound is used for prophylaxis or treatment of osteoporosis, calcium and D3 supplementation are required for maximum benefit.
Chronic administration of many drugs, especially anti-convulsant medications, glucocorticoids, and GnRH ag-onists, are known to produce osteopenia and osteo-porosis. The anticonvulsants inhibit formation of active D3; chronic glucocorticoid therapy increases bone turnover by altering osteoblast differentiation and in-hibiting collagen synthesis; and the GnRH agonists in-duce chemical hypogonadism.
Clinical trials have demonstrated that the use of the bisphosphonates, nasal calcitonin, or human rPTH com-bined with calcium and vitamin D supplementation is effective in preventing drug-induced osteoporosis. Thus, individuals receiving over the long term any medication that can induce osteomalacia should also take one of these compounds and have periodic bone density deter-minations.
Patients with chronic renal failure develop hyperphos-phatemia, hypocalcemia, secondary hyperparathy-roidism, and severe metabolic bone disease. The sec-ondary hyperparathyroidism is thought to be due to hyperphosphatemia and decreased 1, 25-(OH)2 forma-tion. Oral or intravenous 1,25-(OH)2 D3 (calcitriol) ther-apy along with oral phosphate-binding agents and cal-cium supplementation is effective in reducing the effects of renal osteodystrophy.
Paget’s disease is an uncommon disorder of bone char-acterized by mixed lytic and sclerotic bone changes.
These individuals have areas of increased bone resorp-tion and other areas of abnormal new bone formation. The abnormal bone formation can result in pain, defor-mity, and fracture of affected bones. The bisphospho-nates and calcitonin are most commonly used in the treatment of this disease. Long-term continuous use of bisphosphonates can be associated with the induction of osteomalacia through a direct impairment of new bone formation. Therefore, the bisphosphonates are given in a cyclic pattern to treat Paget’s disease.
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