Osteodystrophy

Pseudohypoparathyroidism is characterized by end-organ resistance to parathyroid hormone (98,108). This disease takes various forms, including Albright s hereditary osteodystrophy, which has unusual physical features and a generalized resistance to G-protein-linked hormones that function through cAMP as a second messenger. This defect is associated with a deficiency in the levels of the a-subunit of (109). Because this defect may be generalized, such patients also have olfactory dysfunction (110). 

Osteitis fibrosa cystica Renal osteodystrophy Osteosclerosis Anticonvulsant treatment... 

In the treatment of diseases where the metaboUtes are not being deUvered to the system, synthetic metaboUtes or active analogues have been successfully adrninistered. Vitamin metaboUtes have been successfully used for treatment of milk fever ia catde, turkey leg weakness, plaque psoriasis, and osteoporosis and renal osteodystrophy ia humans. Many of these clinical studies are outlined ia References 6, 16, 40, 51, and 141. The vitamin D receptor complex is a member of the gene superfamily of transcriptional activators, and 1,25 dihydroxy vitamin D is thus supportive of selective cell differentiation. In addition to mineral homeostasis mediated ia the iatestiae, kidney, and bone, the metaboUte acts on the immune system, P-ceUs of the pancreas (iasulin secretion), cerebellum, and hypothalamus. 

Renal osteodystrophy stems from disruptions in calcium, phosphorus, and vitamin D homeostasis through the interaction with the parathyroid hormone. 

What information would you request to determine if the patient has renal osteodystrophy ... 

FIGURE 23-5. Pathogenesis of secondary hyperparathyroidism and renal osteodystrophy in patients with CKD. 

Clinical Presentation of Secondary Hyperparathyroidism and Renal Osteodystrophy ... 

Renal osteodystrophy Altered bone turnover that results from sustained metabolic conditions that occur in chronic kidney disease, including secondary hyperparathyroidism, hyperphosphatemia, hypocalcemia, and vitamin D deficiency. 

Secondary hyperparathyroidism Increased secretion of parathyroid hormone from the parathyroid glands caused by hyperphosphatemia, hypocalcemia, and vitamin D deficiency that result from decreased kidney function. It can lead to bone disease (renal osteodystrophy). 

Patients with end-stage renal disease hyperphosphatemia ineffectively filter excess phosphate that enters the body in the normal diet.278 Elevated phosphate produces the bone disorder renal osteodystrophy. Skeletal deformity may occur, possibly associated with cardiovascular disease. Calcium deposits may further build up around the body and in blood vessels creating further health risks. The use of lanthanum carbonate is being promoted as an alternative to aluminum-based therapies.279,280 Systemic absorption, and cost have produced a clinical candidate, Fosrenol (AnorMED), an intriguing use of a lanthanide compound in therapy. 

Calcium-phosphorus balance is mediated through a complex interplay of hormones and their effects on bone, GI tract, kidney, and parathyroid gland. As kidney disease progresses, renal activation of vitamin D is impaired, which reduces gut absorption of calcium. Low blood calcium concentration stimulates secretion of parathyroid hormone (PTH). As renal function declines, serum calcium balance can be maintained only at the expense of increased bone resorption, ultimately resulting in renal osteodystrophy (ROD) (Fig. 76-7). 

FIGURE 76-7. Pathogenesis of secondary hyperparathyroidism and renal osteodystrophy in patients with chronic kidney disease. These adaptations are lost as renal failure progresses. (Ca, calcium, P04 phosphate PTH, parathyroid hormone.)... 

Ni, Mg, Sr excess Co, Mn deficit South Ural Unbalanced ratio of essential elements in all biogeochemical food webs Endemic osteodystrophy in humans and animals... 

Inactivating G a variants lead to Albright s hereditary osteodystrophy (AHO) in the heterozygote, snggesting that G a haploinsnfficiency canses the disorder. AHO is characterized by short statnre, obesity, brachydactyly (shortening of metacarpal and metatarsal bones), snbcntaneous ossifications, and mental or developmental deficits (86,87). The severity of the phenotype is variable. Some patients with G a mutations have few or no symptoms. 

Patients with advanced renal insufficiency (Ccr less than 30 mL/min) exhibit phosphate retention and some degree of hyperphosphatemia. The retention of phosphate plays a role in causing secondary hyperparathyroidism associated with osteodystrophy and soft-tissue calcification. Calcium acetate, when taken with meals, combines with dietary phosphate to form insoluble calcium phosphate, which is excreted in the feces. 

The pharmacotherapeutic uses of vitamin D include vitamin D deficiencies, rickets in children and osteomalacia in adults, and renal osteodystrophy in patients with chronic renal failure. For metabolic rickets in patients with a deficiency of... 

The treatment of the complications of CRF may occur before or during dialysis. They include pericarditis, congestive heart failure, hypertension, hemopoietic abnormalities and renal osteodystrophy. 

Renal osteodystrophy is a complex disorder with several pathogenic factors. Histological evidence of bone disease is common in early renal failure and deficits in calcitriol synthesis seems to be an important factor in the pathogenesis of secondary hyperparathyroidism in early CRF. The most common component is osteitis fibrosa manifested as subperiosteal resorption of bone. This is due to decreased excretion as well as increased secretion of parathyroid hormone. In CRF small increments of serum phosphorus cause small decreases in serum calcium. 

Patients with chronic renal failure develop hyperphosphatemia, hypocalcemia, secondary hyperparathyroidism, and severe metabolic bone disease. The secondary hyperparathyroidism is thought to be due to hyperphosphatemia and decreased 1, 25-(OH)2 formation. Oral or intravenous l,25-(OH)2D3 (calcitriol) therapy along with oral phosphate-binding agents and calcium supplementation is effective in reducing the effects of renal osteodystrophy. 

Nutritional rickets PO 0.5 mg as a single dose or 13-50 mcg/day until healing occurs. Renal osteodystrophy PO 0.25-0.6 mg/24 hr adjusted as necessary to achieve normal serum calcium levels and promote bone healing. 

Vitamin D analog of choice for prevention and treatment of renal osteodystrophy less expensive than calcitriol... 

Musculoskeletal Effects. Histological examination of tissues from the musculoskeletal system of rats and mice exposed to 2,3-benzofuran by gavage for up to 2 years showed a compound-related increase in bone degeneration (fibrous osteodystrophy) in chronically-exposed male rats (NTP 1989). The observed increase in bone degeneration, which was not statistically significant at doses of either 30 or 60 mg/kg/day, was not considered a direct effect of 2,3-benzofuran exposure, but as secondary to calcium and phosphate imbalance due to increased severity of nephropathy in male rats caused by... 

It is indicated in osteoporosis, hypoparathyroidism, hyperparathyroidism (with bone disease), renal osteodystrophy, nutritional and malabsorptive rickets, hypophosphataemic vitamin D resistant rickets and osteomalacia. 

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