Endo - Calcium and Bone Disease I & II

Mainstay of therapy for hypercalcemia. The bisphosphonates are taken up by mineralized bone matrix where they inhibit osteoclast action.

The bisphosphonate currently approved in the US for treatment of hypercalcemia is pamidronate.

Bisphosphonate used for treatment of hypercalcemia. After intravenous administration of pamidronate, serum calcium falls within 2-5 days, and usually remains normal for up to one week.

Pamidronate has been shown to normalize serum calcium levels in 70% of patients with malignancy associated hypercalcemia.

Osteogenesis imperfecta

It is a primary osteoblast disease. An inherited connective tissue disease characterized by osteopenia, fragile bones, hyperextensible joints, dental abnormalities, bluish discoloration of the sclera and adult onset hearing loss. It is caused by mutations in the type 1 collagen gene, resulting in qualitative or quantitative abnormality the most abundant protein in bone, type 1 collagen. OI has a reported incidence of 1/20,000 to 1/60,000 live births.

Cancers can cause hypercalcemia by several different pathophysiologic mechanisms: direct boney metastases, elaboration of parathyroid hormone-related polypeptide (PTHrP), cytokine production associated with osteoclast activation, increased 1,25 VitD3 production (lymphomas) and rarely ectopic PTH production.

Serum PTH is almost always low in malignancy associated hypercalcemia.

Caused by patients taking in excess amounts of milk and antacids (calcium carbonate) to control their dyspepsia. Alkalosis impairs the renal ability to excrete calcium. PTH is suppressed.

There is always an underlying renal disease in Milk-Alkali syndrome

Decreased amounts of bone mineral (calcification) seen on the radiograph. Bone mineral density between 1.0 and 2.5 standard deviations below peak bone mineral density on DXA.

An example of a primary osteoclast disease, resulting in skeletal fragility in spite of impairment in bone resorption. Whatever the precise molecular mechanism, whether failure of osteoclast differentiation or of osteoclast function, the impact on bone tissue is inability to model and remodel effectively, leading to deficient mechanical performance.

Decreased and defective bone mass. Bone density is > 2.5 standard deviation below peak bone density on DXA. It is a skeletal disorder characterized by compromised bone strength (bone density + bone quality) predisposing to an increased risk of fracture.

Rare before age 60, this is a disorder of bone remodeling leading to abnormal bone formation and clinically presents as bone pain, bowing deformities of the long bones, enlargement of the skull and increased bone vascularity. The exact cause is unknown, although viral infection of osteoclasts has been implicated. Treatment is pulse therapy with bisphosphonates every 3-6 months depending upon the severity of the disease.

The peptide responsible for the syndrome of HHM (humoral hypercalcemia of malignancy). Frequent with squamous cell cancers, renal cell and breast cancers. PTH level suppressed for degree of hypercalcemia.

PTHrP mimics many biological actions of PTH and binds to PTH receptors. It causes increased renal reabsorption of calcium, increased osteoclastic bone resorption, but does NOT stimulate 1 renal hydroxylase, therefor, no increase in 1,25 OH VitD levels.