Bone Disease

Although historically most patients with normocalcemic hyperparathyroidism were identified because of renal calculi, an increasing number of patients have recently been identified by screening patients for osteoporosis with dual-energy x-ray absorptiometry (DEXA) scans.

Traditionally, hyperparathyroidism was associated with overt bone disease in a significant number of patients. This traditional bone disease was frequently symptomatic and associated with radiologic findings such as bone cysts, brown tumors of the long bones, subperiosteal resorption of the distal phalanges and clavicles, and "salt and pepper" demineralization of the skull. The increased awareness of the diagnosis of PHPT and multichannel blood screening studies have resulted in an earlier diagnosis of this condition and considerably fewer patients with these classic bone findings. The introduction of screening for osteoporosis with DEXA scans has identified an increasing number of patients with severe osteopenia or osteoporosis.39 Hyperparathyroidism is considered an important cause of osteoporosis as a consequence of its known catabolic effect promoting osteoclast activity and bone resorption. The human skeleton consists of cortical and trabecular bone. Cortical bone is the compact layer, which predominates in the shafts of the long bones. Trabecular bone is composed of a series of thin plates, which form the interior meshwork of bones, particularly the vertebrae, pelvis, and end of long bones. The major site of bone mineral loss in PHPT appears to be cortical bone; therefore, the DEXA scan of the distal radius is more sensitive than that of the spine or hip in detecting bone loss due to PHPT.40 The diagnosis of PHPT should be pursued in patients with severe osteopenia or osteoporosis because of the favorable outcome of parathyroid surgery. Correction of PHPT results in stopping the accelerated bone loss attributable to the hyperparathyroidism and a 10% to 12% increase in bone mass in trabecular as well as in cortical bone. This increase lasts at least a decade after successful parathyroid surgery 40 Patients with a low vertebral bone density demonstrated a marked increase in bone density after surgery. This group experienced a 20% increase in vertebral bone density over a 4-year period.41 This indicates that remineralization after surgical correction of PHPT involves a generalized increase in bone mass, not just cortical bone mass.

Minimal, intermittent, or no elevation of the total calcium in patients with PHPT and osteoporosis is not uncommon. A study at Rhode Island Hospital identified 64 patients from

January 1995 to June 1999 with osteoporosis defined by a t score of 2.5 or less who underwent parathyroid surgery. Fifteen (23%) of these patients had 40% of their preoperative total calcium values within the normal range and 6 (9%) of these patients had no preoperative elevated total calcium, These 6 patients had a total of 44 concomitant serum ionized and total calcium measurements; 42 of the ionized calcium values were elevated and 2 were normal. Each of these patients had at least one elevated value for iPTH.43

Patients with severe osteopenia or osteoporosis who do not have an elevated serum total calcium should be screened on 3 consecutive days for serum ionized and total calcium and a serum iPTH on at least 1 day to minimize the risk of missing the diagnosis of normocalcemic hyperparathyroidism.

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