A 46-year-old woman is hospitalized for recurrent renal colic. She has passed 2 urinary stones during the last 2 years. The most recent stone contained 80% calcium phosphate and 20% calcium oxalate. The patient also has diffuse aches and pains and has a history of peptic ulcer disease, for which she takes famotidine daily. Laboratory results are as follows:
| Serum sodium | 140 mEq/L |
| Serum potassium | 4.0 mEq/L |
| Serum chloride | 103 mEq/L |
| Serum creatinine | 0.8 mg/dL |
| Serum calcium | 12.0 mg/dL |
| Serum phosphorus | 2.4 mg/dL |
| 24-hour urinary calcium excretion | 350 mg (normal: 100-300) |
Which of the following changes in bone structure is most likely associated with this patient's condition?
This patient with recurrent calcium nephrolithiasis and hypercalcemia most likely has primary hyperparathyroidism (PHPT). Besides kidney stones, classic manifestations include bone pain, gastrointestinal disturbances (eg, peptic ulcer disease), and psychiatric symptoms (ie, "bones, stones, abdominal groans, and psychologic moans"). However, asymptomatic hypercalcemia is the most common presentation. 85% of cases are caused by a parathyroid adenoma, but PHPT can also be due to parathyroid hyperplasia or, rarely, parathyroid cancer.
Excess parathyroid hormone causes hypercalcemia via the following mechanisms:
Patients usually also have hypophosphatemia due to decreased phosphate reabsorption in the proximal renal tubules.
Because of the increased bone resorption, PHPT often leads to osteoporosis. However, unlike the typical osteoporosis of aging, which predominantly affects trabecular bone, osteoporosis in PHPT is most pronounced in the cortical (compact) bone of the appendicular skeleton (eg, pectoral girdle, pelvic girdle, limbs). Cortical thinning is characteristic and appears radiologically as subperiosteal erosions. More advanced disease can present as osteitis fibrosa cystica, characterized by granular decalcification of the skull ("salt-and-pepper skull"), osteolytic cysts, and brown tumors.
(Choice A) Disorganized lamellar bone in a mosaic pattern is a characteristic finding in Paget disease of bone. Serum calcium and phosphorus are normal in these patients.
(Choice B) Osteoid matrix accumulation around trabeculae is seen in vitamin D deficiency. Histologically, there is excessive unmineralized osteoid with widened osteoid seams. Patients typically have low urinary calcium.
(Choice C) Osteopetrosis ("marble bone disease") is characterized by persistence of the primary spongiosa in the medullary cavity with no mature trabeculae. It is caused by decreased osteoclastic bone resorption, resulting in accumulation of woven bone and diffuse skeletal thickening.
(Choice E) Trabecular thinning with fewer interconnections is characteristic of postmenopausal osteoporosis. Although long-standing PHPT causes thinning of cortical bone, the trabecular architecture remains relatively preserved.
Educational objective:
Increased bone resorption in primary hyperparathyroidism leads to osteoporosis primarily involving the cortical bone of the appendicular skeleton. The cortical thinning appears radiologically as subperiosteal erosions. More advanced disease can present as osteitis fibrosa cystica (ie, granular decalcification of the skull, osteolytic cysts, and brown tumors).