A 75-year-old man comes to the office for a routine preventive examination. He has no ongoing symptoms. The patient's medical history is significant for osteoarthritis, hypertension, and hyperlipidemia. Current medications include hydrochlorothiazide and atorvastatin. He does not smoke and consumes 1 or 2 beers on weekends. The patient walks 2 miles every morning and eats a balanced diet. Vital signs are within normal limits. His cardiopulmonary examination is normal, and his abdomen is soft and nontender. Rectal examination shows a diffusely enlarged prostate without nodules. The distal interphalangeal joints are enlarged, and his gait is normal. Laboratory results are as follows: Which of the following is the most likely cause of the elevated alkaline phosphatase in this patient?

Question

A 75-year-old man comes to the office for a routine preventive examination.  He has no ongoing symptoms.  The patient's medical history is significant for osteoarthritis, hypertension, and hyperlipidemia.  Current medications include hydrochlorothiazide and atorvastatin.  He does not smoke and consumes 1 or 2 beers on weekends.  The patient walks 2 miles every morning and eats a balanced diet.  Vital signs are within normal limits.  His cardiopulmonary examination is normal, and his abdomen is soft and nontender.  Rectal examination shows a diffusely enlarged prostate without nodules.  The distal interphalangeal joints are enlarged, and his gait is normal.  Laboratory results are as follows:  Which of the following is the most likely cause of the elevated alkaline phosphatase in this patient?

Quizplus · Accepted Answer

11ec25c8_d121_e879_bc81_0dd202f120d8_MD0003_00 Alkaline phosphatase is a ubiquitous enzyme that has its highest expression in bone and hepatobiliary tissues. It is a useful marker for cholestatic liver disease and diseases of bone causing increased bone turnover and new bone formation. The most common cause of an isolated, asymptomatic elevation of alkaline phosphatase in an elderly patient is Paget disease of bone (osteitis deformans). Paget disease is caused by osteoclast dysfunction, with defective osteoid formation, increased bone remodeling, and focal hypertrophy (eg, enlarged distal interphalangeal joints in this patient). The most commonly affected bones are the skull, clavicles, pelvis, and long bones. Although the classic clinical manifestations are related to areas of anatomic involvement (eg, hearing loss due to cochlear involvement, radiculopathy due to nerve compression), Paget disease is most frequently discovered incidentally on routine blood tests. Alkaline phosphatase levels can be strikingly elevated, often >10 times the upper limit of normal. Fractionation of alkaline phosphatase would show a predominance of bone rather than liver isoenzymes. Laboratory markers for bone turnover (eg, procollagen type I N propeptide, urine hydroxyproline) are frequently elevated. X-rays of affected bones will show osteolytic or mixed lytic-sclerotic lesions, and radionuclide bone scan is useful to fully stage the disease. (Choices A and B) Statins (eg, atorvastatin) can cause minor elevations in liver markers, but this typically manifests with a hepatocellular pattern (predominant elevations in transaminases) rather than a cholestatic pattern (predominant elevation in alkaline phosphatase). Alcoholic liver disease also is typically associated with a hepatocellular pattern, classically with a 2:1 ratio of aspartate aminotransferase to alanine aminotransferase. (Choice C) Prostate cancer with bone metastasis may cause an elevation of alkaline phosphatase but will usually cause additional features such as bone pain or systemic symptoms (eg, weight loss, fatigue). Also, prostate-specific antigen will usually be >4 ng/mL, and prostate nodularity or asymmetry may be palpable on examination. Diffuse (smooth) prostatic enlargement is common in older men and is usually benign. (Choice E) Multiple myeloma typically presents with bone pain and systemic symptoms. However, calcium is usually elevated, renal dysfunction is often present, and alkaline phosphatase is typically normal. Educational objective: The most common cause of an asymptomatic elevation of alkaline phosphatase in an elderly patient is Paget disease of bone, which is frequently discovered incidentally on routine blood tests. X-rays will show osteolytic or mixed lytic-sclerotic lesions, and radionuclide bone scan can fully stage the disease.

A 75-Year-Old Man Comes to the Office for a Routine