A 68-year-old man presents to the clinic complaining of mild, intermittent aching in his r… — USMLE Step 3

A $68$ -year-old man presents to the clinic complaining of mild, intermittent aching in his right thigh over the past several months. He attributed the pain to "getting older" but mentions it occasionally wakes him up at night. He has no other systemic symptoms and his medical history is significant only for hypertension, for which he takes lisinopril. Vital signs are within normal limits. Physical examination is unremarkable, with no localized bone tenderness, joint instability, jaundice, or hepatomegaly.

Laboratory results are as follows:

Test	Result	Reference Range
Calcium	$9.5$ mg/dL	$8.4$ - $10.2$ mg/dL
Phosphorus	$3.6$ mg/dL	$2.7$ - $4.5$ mg/dL
Total bilirubin	$0.9$ mg/dL	$0.2$ - $1.2$ mg/dL
Alkaline phosphatase	$410$ U/L	$40$ - $120$ U/L
Aspartate aminotransferase (AST)	$22$ U/L	$8$ - $40$ U/L
Alanine aminotransferase (ALT)	$26$ U/L	$8$ - $40$ U/L
Gamma-glutamyl transferase (GGT)	$28$ U/L	$8$ - $61$ U/L
Prostate-specific antigen (PSA)	$1.5$ ng/mL	$\leq 4.0$ ng/mL

Which of the following is the most likely diagnosis based on this patient's laboratory findings?

Paget disease of boneAnswer
B
Primary biliary cholangitis
C
Osteomalacia
D
Multiple myeloma
E
Primary hyperparathyroidism

Answer

Paget disease of bone

The correct diagnosis is Paget disease of bone. The patient presents with a significantly elevated alkaline phosphatase. Because alkaline phosphatase is produced by both bone osteoblasts and biliary epithelium, checking gamma-glutamyl transferase (GGT) is the required first step to determine its origin. The patient's normal GGT level confirms that the alkaline phosphatase elevation is of bone origin. Once a bone source is established, serum calcium and phosphorus must be evaluated. In Paget disease of bone, the localized acceleration of bone remodeling leads to isolated elevations in alkaline phosphatase, while systemic calcium and phosphorus homeostasis remains completely normal. This patient's normal calcium (

9.5

mg/dL) and normal phosphorus (

3.6

mg/dL) combined with his clinical presentation of deep thigh pain strongly support this diagnosis.

Step-by-Step Solution

Assess the elevated alkaline phosphatase level in relation to the gamma-glutamyl transferase (GGT) level.

The alkaline phosphatase is significantly elevated at

410

U/L, but the GGT is normal at

28

U/L.

Alkaline phosphatase is derived from both bone osteoblasts and the hepatobiliary system. A normal GGT confirms that the origin of the elevation is bone and successfully rules out a cholestatic liver process.

Evaluate serum calcium and phosphorus levels to narrow the differential diagnosis of the bone disorder.

Both serum calcium (

9.5

mg/dL) and phosphorus (

3.6

mg/dL) are strictly within normal limits.

Differentiating among metabolic bone diseases requires these markers. Osteomalacia typically presents with low calcium and phosphorus, while primary hyperparathyroidism presents with high calcium and low phosphorus.

Synthesize the demographic and laboratory data to determine the most likely diagnosis.

An isolated elevated bone alkaline phosphatase with completely normal calcium and phosphorus in an elderly male with localized bone pain is highly indicative of Paget disease of bone.

Paget disease causes localized, accelerated bone remodeling that increases alkaline phosphatase (due to osteoblastic activity) without systemically altering calcium or phosphorus homeostasis.

Key Concept

Isolated elevation of alkaline phosphatase with a normal gamma-glutamyl transferase (GGT) indicates a bone origin. When accompanied by normal serum calcium and phosphorus, it is highly indicative of Paget disease of bone.

Question

Answer

Step-by-Step Solution

Key Concept

Common Mistakes

Topics

More questions from this topic