A 64-year-old woman is evaluated for right hand pain after a fall from standing height. The patient has a 20-year history of type 2 diabetes mellitus complicated by diabetic nephropathy and advanced chronic kidney disease. X-ray of the right hand reveals no fractures, but it demonstrates subperiosteal resorption and new bone formation, particularly at the radial aspect of the middle phalanges. Laboratory studies show elevated serum parathyroid hormone, alkaline phosphatase, and phosphorus levels. If a bone biopsy is performed, which of the following findings would most likely be present in this patient?
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Parathyroid hormone (PTH) plays an important role in bone remodeling by regulating the activity of osteoblasts (which secrete osteoid for bone formation) and osteoclasts (which resorb bone). PTH exerts the following dual effects on bone:
Increases bone formation by stimulating the differentiation and activity of osteoblasts
Increases bone resorption by transforming osteoblasts into osteoclasts
This balanced process allows for normal bone turnover but can become disrupted in conditions that alter PTH secretion, such as secondary hyperparathyroidism in patients with chronic kidney disease (CKD). In CKD, hypocalcemia, caused by decreased formation of active vitamin D and decreased renal phosphate excretion, triggers PTH secretion in an attempt to increase serum calcium. Despite releasing calcium from bones, this compensatory response is unable to fully normalize serum calcium (due to the failing kidneys) and therefore results in chronic PTH elevation (ie, loss of negative feedback).
Chronic PTH elevation leads to increased activity of both osteoclasts and osteoblasts; the increase in osteoclast activity exceeds that of osteoblasts, which results in greater bone resorption than formation (suggested by an elevated serum alkaline phosphatase). A potential consequence of this high bone turnover is osteitis fibrosa cystica, a form of renal osteodystrophy characterized by weakened bone caused by the replacement of mineralized bone with fibrous tissue.
Serum elevations in PTH, phosphorus, and alkaline phosphatase, in conjunction with the plain radiography finding of subperiosteal resorption, are typically sufficient for the diagnosis of osteitis fibrosa cystica. However, a bone biopsy would show an increased number of osteoclasts and osteoblasts throughout the bone trabeculae (Choice D).
(Choice A) Excessive treatment of hyperparathyroidism can lead to chronically low PTH levels, which can cause adynamic bone disease. Adynamic bone disease is another form of renal osteodystrophy characterized by a low bone turnover state with decreased cellularity (ie, decreased numbers of both osteoblasts and osteoclasts).
(Choice B) The combination of decreased osteoclasts and increased osteoblasts is rarely seen in bone disease.
Educational objective:
Osteitis fibrosa cystica is a form of renal osteodystrophy characterized by abnormally high bone turnover caused by chronic parathyroid hormone stimulation of osteoclasts to a greater degree than that of osteoblasts. Bone biopsy would show an increased number of both osteoclasts and osteoblasts.