A 68-year-old woman comes to the office due to a 1-year history of right leg pain. The pain has a relatively constant severity and has not responded to over-the-counter medications. The patient has also experienced intermittent headaches over the last 6 months. Medical history is notable for hypertension, diet-controlled diabetes mellitus, and acute cholecystitis for which she underwent cholecystectomy 5 years ago. Her current medications include amlodipine and as-needed acetaminophen. The patient does not smoke, and she drinks 1 or 2 alcoholic beverages a night. Vital signs are normal. The hip and knee have normal range of motion with no gross deformity. X-ray of the skull reveals areas of bone resorption and sclerosis. X-ray of the leg reveals cortical thickening with mild bowing. Which of the following are the most likely findings on laboratory evaluation?

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11ec25c8_d512_aac0_bc81_850f5b555cd4_MD0003_00 This patient has typical features of Paget disease of bone, including bony pain, deformity, and mixed lytic/sclerotic lesions on x-ray. Paget disease is characterized by disordered osteoclastic bone resorption of uncertain etiology. Paget disease can cause focal enlargement, weakness, or fracture of bone. Bowing of long bones, bone pain, and arthritis in adjacent joints are common. Involvement of cranial bones may cause frontal bossing, headaches, cranial nerve dysfunction, and hearing loss. Due to the increased bone turnover, serum alkaline phosphatase (bone isoenzyme) is elevated, often >10 times the upper limit of normal. Paget disease is the most common cause of an asymptomatic elevation in alkaline phosphatase in older patients and is often discovered on routine laboratory testing. Urine hydroxyproline is derived almost exclusively from the breakdown of collagen, and levels will be increased in Paget disease as well. Urine calcium may be increased. However, serum calcium and phosphorus levels will usually be normal in the absence of other complicating factors (eg, prolonged immobility, concurrent hyperparathyroidism). (Choice A) Multiple myeloma can cause osteolytic lesions seen on x-ray along with hypercalcemia and laboratory evidence of bone turnover. However, bony sclerosis, bowing, and cortical thickening would not be seen. (Choice B) Elevated calcium, low phosphorus, and elevated alkaline phosphatase would be seen in primary hyperparathyroidism. Urine hydroxyproline is commonly elevated, not normal. (Choice C) Hypercalcemia in the setting of normal phosphorus and alkaline phosphatase levels may be observed in milk-alkali syndrome, which is due to ingestion of large amounts of calcium and alkali (eg, calcium carbonate). (Choice D) Hypocalcemia with hyperphosphatemia suggests hypoparathyroidism, which is most commonly seen following thyroid or other neck surgery. Potential manifestations include paresthesias, carpopedal spasm, and seizures. (Choice F) Normal calcium, phosphorus, and bone marker levels would be seen in osteoarthritis. Patients may present with musculoskeletal pain, but radiologic findings would be confined to joints and periarticular bone. Educational objective: Paget disease of bone is characterized by disordered osteoclastic bone resorption. Serum alkaline phosphatase and urine hydroxyproline levels are increased due to increased bone turnover. Serum calcium will usually be normal in the absence of other complicating factors.

A 68-Year-Old Woman Comes to the Office Due to a 1-Year