A 25-year-old man comes to the office due to bilateral hip pain for the last 6 months. The pain started insidiously and has progressively worsened to the point where he has difficulty walking. The patient has no history of trauma. Medical history is significant for a seizure disorder, for which he has taken phenytoin for the past 5 years. The patient does not use tobacco or alcohol. X-ray of the hip joint shows bilateral, symmetric, narrow radiolucent lines of 2-3 mm in width with sclerotic borders as well as diffuse cortical thinning. Which of the following is the most likely cause of this patient's current condition?

Question

A 25-year-old man comes to the office due to bilateral hip pain for the last 6 months.  The pain started insidiously and has progressively worsened to the point where he has difficulty walking.  The patient has no history of trauma.  Medical history is significant for a seizure disorder, for which he has taken phenytoin for the past 5 years.  The patient does not use tobacco or alcohol.  X-ray of the hip joint shows bilateral, symmetric, narrow radiolucent lines of 2-3 mm in width with sclerotic borders as well as diffuse cortical thinning.  Which of the following is the most likely cause of this patient's current condition?

Quizplus · Accepted Answer

11ec160b_3bc5_c2a5_9249_85ee2d347188_MD0001_00 This patient has osteomalacia, presenting with hip pain and symmetric linear radiolucencies (Looser zones) and cortical thinning on x-ray. Osteomalacia is most commonly due to vitamin D deficiency, which reduces intestinal calcium absorption, leading to secondary hyperparathyroidism and renal phosphate wasting. The resulting hypophosphatemia causes impaired mineralization of the osteoid matrix. Although bone contours are generally normal, the newly formed bone is prone to fracture (Looser zones likely represent a type of insufficiency fracture). Vitamin D is normally obtained from the diet as well as through conversion from 7-dehydrocholesterol by ultraviolet light in the skin. In the liver, it is converted to 25-hydroxyvitamin D. Subsequently, it is converted to 1,25-dihydroxyvitamin D (the active form) by 1-alpha-hydroxylase in the kidneys. Catabolism of vitamin D is initiated by CYP24A1 (also called 24-hydroxylase), which acts on both the 25- and 1,25-hydroxylated forms. Expression of this enzyme is induced by phenytoin and other anticonvulsants (eg, carbamazepine), which can lead to increased breakdown of vitamin D and vitamin D deficiency. Patients taking long-term anticonvulsant therapy (eg, carbamazepine, phenytoin) therefore require vitamin D supplementation. (Choice A) Estrogen maintains bone mass in both women and men by inducing production of osteoprotegerin by osteoblasts and stromal cells and decreasing expression of receptor activator of nuclear factor kappa-B on osteoclast precursors. Aromatase inhibitors (eg, anastrozole) can cause osteoporosis by reducing local concentrations of estrogen in bone. (Choice B) Bisphosphonates inhibit osteoclast activity, leading to reduced bone resorption. Chronic use leads to reduced bone remodeling with decoupling of resorption and new bone formation. This may increase the risk for atypical (eg, transverse shaft) femoral fracture, but this effect is not seen with anticonvulsants. (Choice C) Excessive fecal loss of phosphate can cause hypophosphatemia, and over time can lead to bone loss and fracture. This is typically seen with chronic use of nonabsorbable antacids (eg, aluminum hydroxide), which bind phosphate in the intestine to form insoluble complexes. Educational objective: Catabolism of vitamin D is initiated by CYP24A1 (also called 24-hydroxylase). Expression of this enzyme is induced by phenytoin and other anticonvulsants (eg, carbamazepine), which can lead to increased breakdown of vitamin D and vitamin D deficiency.

A 25-Year-Old Man Comes to the Office Due to Bilateral