What disorders are associated with low turnover bone disease?
Low-turnover or adynamic bone disease is defined by the presence of low or absent bone formation as determined by decreased tetracycline uptake into bone, in conjunction with a paucity of bone-forming osteoblasts and bone-resorbing osteoclasts (decreased T).
It may also be associated with a defect in mineralization (abnormal M), resulting in the histologic lesion referred to as osteomalacia. Bone volume (V) is variable. Clinically it may manifest with nonspecific bone pain and fractures. PTH concentrations are relatively low (less than 100 to 200 pg/mL), and hypercalcemia is a common feature.
There may be a tendency for increased extraskeletal calcification. Low turnover is characterized histologically by absence of cellular (osteoblast and osteoclast) activity, osteoid formation, and endosteal fibrosis. This is a disorder of decreased bone formation, accompanied by a secondary decrease in bone mineralization. Low turnover disease was initially described as a result of aluminum toxicity.
Aluminum bone disease is diagnosed by special staining, which demonstrates the presence of aluminum deposits at the mineralization front. Outside of aluminum, the major risk factors for low turnover bone disease include diabetes, aging, and malnutrition. The other causes of low bone formation in CKD are multifactorial and include:
• Vitamin D deficiency
• High serum phosphate
• Metabolic acidosis
• Elevated circulating cytokine levels (interleukin [IL]-I, tumor necrosis factor [TNF])
• Low estrogen and testosterone levels
Normal or mildly elevated serum PTH concentrations have been associated with adynamic bone disease, as there is a resistance to the bone stimulatory effect of PTH in CKD. PTH receptor downregulation is one potential mechanism to explain the bone resistance effect to PTH resulting, in part, from persistently elevated PTH.
