Bone/Parathyroid Case 5

A 55-year-old male patient presents to your clinic for evaluation of back pain which started 2 weeks ago. Treatment with OTC non-steroidal anti-inflammatory agent has not provided relief. Patient has history of lymphoma which was treated with chemotherapy in the past and is cancer free now. A plain film of lumbar spine shows a compression fracture of L4 vertebra with significant height loss. A clinical diagnosis of osteoporosis is made while pending further diagnostic testing with DXA scan. 

Examination shows sparse body and facial hair, mild gynecomastia and small testicles on both sides. Gonadal labs show a fasting, morning total testosterone of 145 ng/dL with LH of 35, low 25 OH vitamin D at 18 g/ml. along with mild normocytic anemia. Other biochemical laboratory tests are normal. 

Question 1

What is not associated with high fracture risk in this patient?

A. Low T score
B. Low TBS score
C. Low estrogen level
D. High estrogen level because of presence of gynecomastia
E. Low 25-hydroxy vitamin D level
Correct Answer
D. High estrogen level because of presence of gynecomastia

Hypogonadal men usually have lower estrogen levels and not high level which adds to fracture risk due to bone loss. Gynecomastia is associated with change in the ratio of estrogen/testosterone in favor of estrogen and not due to absolute increase in estrogen.  

Androgens promote the proliferation and differentiation of osteoblasts, as well as inhibit osteoclast activity resulting in decreased bone density. Androgens mediate recruitment and signaling of both osteoblasts and osteoclasts, promoting the former and inhibiting the latter. Androgens also get converted to estrogen by aromatase enzyme which is found in bone along with other tissues. Estrogen is the final mediator of bone turnover in both genders. It inhibits bone resorption, principally by directs effects on osteoclasts, although effects of estrogen on osteoblast proliferation and activation also play a role. A decrease in estrogen level in hypogonadal men such as this patient, due to reduced levels of substrate testosterone, contribute to bone loss and fracture risk. Even though there is a relative reduction of estrogen in hypogonadal men, the ratio of estrogen to testosterone is altered and is high which results in gynecomastia. In primary hypogonadism, high FSH also potentiates aromatase activity. Besides, low estrogen promoting bone loss, fracture risk is also higher in hypogonadal men due to sarcopenia fall risk and reduced exercise ability.