Paget’s disease hypercalcemia

Use calcium metabolism regulator (treatment of Paget s disease, hypercalcemia of malignancy)... 

Tiludronate (Sanofi Winthrop) Paget s disease Hypercalcemia of malignancy Tumoral osteolysis Osteoporosis -10 1995 31,350... 

Calcitonin is secreted when abnormally high calcium levels occur in plasma. Although plasma concentrations are normally minute (<100 pg/mL), they increase two- to threefold after calcium infusion. Calcitonin has a short plasma half-life (ca 10 min). Certain thyroid tumors are the result of CT concentrations 50—500 times normal. The mechanism of action is a direct inhibition of bone resorption. Calcitonin is used clinically in various diseases in which hypercalcemia is present, eg, Paget s disease (46). 

The answer is c. (Hardman, p 15230 Administration of intravenous CaG would immediately correct the tetany that might occur in a patient in whom a thyroidectomy was recently performed. Parathyroid hormone would act more slowly but could be given for its future stabilizing effect. Long-term control of a patient after a thyroidectomy can be obtained with vitamin D and dietary therapy Calcitonin is a hypocalcemic antagonist of parathyroid hormone. Plicamycin (mithramycin) is used to treat Paget s disease and hypercalcemia. The dose employed is about one-tenth the amount used for plicamycin s cytotoxic action. 

Bisphosphonates structurally mimic endogenous pyrophosphate, which inhibits precipitation and dissolution of bone minerals. They retard bone resorption by osteoclasts and, in part, also decrease bone mineralizatioa Indications include tumor osteolysis, hypercalcemia, and Paget s disease. Qinical trials with etidronate, administered as an intermittent regimen, have yielded favorable results in osteoporosis. With the newer drugs clodronate, pamidronate, and alendronate, inhibition of osteoclasts predominates a continuous regimen would thus appear to be feasible. 

The bisphosphonates are synthetic organic compounds that are incorporated directly into the hydroxyapatite of bone and then inhibit osteoclastic bone resorption. This antiresorptive action makes them useful in the pharmacological treatment of hypercalcemia, osteoporosis, and Paget s disease. 

Multiple bisphosphonates compounds are available for both oral and intravenous use. Some [alendronate (Fosamax) and etidronate (Didronel)] are used for osteoporosis, others [etidronate, tirludronate (Skelid), risedronate Actonel) for Paget s disease, and yet others [pamidronate Aredia), zoledronic acid] for the hypercalcemia of malignancy. 

Calcitonin—Paget s disease and hypercalcemia Estrogens Glucocorticoids Biphosphonates—postmenopausal osteoporosis Eluoride... 

Etidronate and the other bisphosphonates exert a variety of effects on bone mineral homeostasis. In particular, bisphosphonates are useful for the treatment of hypercalcemia associated with malignancy, for Paget s disease, and for osteoporosis (see Newer Therapies for Osteoporosis). Contrary to expectations, some of the newer bisphosphonates appear to increase bone mineral density well beyond the 2-year period predicted for a drug whose effects are limited to blocking bone resorption. The bisphosphonates exert a variety of other cellular effects, including inhibition of l,25(OH)2D... 

Plicamycin is a cytotoxic antibiotic (see Chapter 54) that has been used clinically for two disorders of bone mineral metabolism Paget s disease and hypercalcemia. The cytotoxic properties of the drug appear to involve its binding to DNA and interruption of DNA directed RNA synthesis. The reasons for its usefulness in the treatment of Paget s disease and hypercalcemia are unclear but may relate to the need for protein synthesis to sustain bone resorption. The doses required to treat Paget s disease and hypercalcemia are about one tenth the amounts required to achieve cytotoxic effects. 

Etidronate (Procter Gamble) Paget s disease (Later hypercalcemia heterotopic ossification) 1 <1982 ... 

Pamidronate (Ciba Geigy) Hypercalcemia of malignancy Tumoral osteolysis Paget s disease Osteoporosis -100 1987 25, 312... 

Alendronate is an aminobisphosphonate with general properties similar to those of the other bisphosphonates. It inhibits bone resorption and is nsed in osteoporosis and Paget s disease of bone. It has also been nsed in the treatment of bone metastases and hypercalcemia of malignancy. 

Clodronate is a bisphosphonate that has demonstrated efficacy in patients with a variety of disorders of enhanced bone resorption, including Paget s disease, osteolytic bone metastases, and hypercalcemia of malignancy (8,9). In preclinical studies, clodronate prevented bone loss during immobilization (10). 

Calcitonin inhibits osteoclastic bone resorption, increases the urinary excretion of calcium and phosphate, and reduces serum calcium. It is established in the treatment of disorders of high bone turnover, including Paget s disease and postmenopausal osteoporosis, but is less effective than the bisphosphonates. Calcitonin is less effective than other therapeutic measures in the treatment of acute hypercalcemia. Long-term administration of calcitonin reduces morbidity in cases of osteogenesis imperfecta... 

Trade name Aredia (Novartis) Indications Hypercalcemia, Paget s disease Category Bisphosphonate Half-life 1.6 hours... 

Drugs have also been associated with osteomalacia. Anticonvulsants increase the hepatic cataboHsm of vitamin D metabolites, and produce end-organ resistance. Phosphatebinding antacids used for treatment of peptic ulcer disease cause osteomalacia by preventing the intestinal absorption of phosphate. Etidronate treatment (e.g., of Paget s disease, osteoporosis, or hypercalcemia of mafignancy) can cause a mineralization defect and result in osteomalacia. 

Fraser WD, Logue FC> Gallacher SJ, O Reilly DS, Beastall GH, Ralston SH, et al. Direct and mdirect assessment of the parathyroid response to pamidronate therapy in Paget s disease of bone and hypercalcemia of malignancy. Bone Miner 1991 12 113-21. 

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