Working Diagnosis:
Pathologic hip fracture due to underlying osteoporosis in the setting of subclinical/compensated hypergonadotropic hypogonadism.

Treatment:
The patient was started on high dose vitamin D replacement therapy and referred to physical therapy for rehabilitation.

Testosterone replacement therapy was discussed, however was not initiated due to patient's desire for fertility. Lastly, patient was offered a varicocelectomy, however patient declined procedure.

Outcome:
The patient was found to have elevated 25-OH vitamin D levels (113 ng/mL) after 12 weeks of high dose replacement. His dose was adjusted and continued daily for an additional three months with a 25-OH vitamin D goal of 39.0 ng/mL. On his 12 month follow up, his 25-OH vitamin D level normalized to 56.7 ng/mL. After a year of normalized 25-OH vitamin D level, a DEXA scan was repeated with minimal changes to Z-scores. Repeat lumbar spine Z-score = -2.1 (2.9% increase), femoral neck Z-score= -2.1 (unchanged), and hip Z-score= -2.0 (not statistically significant decrease). He was continued on vitamin D supplementation indefinitely.

The patient also followed up with orthopedics over a 13 month period after the fracture. He had appropriate pin placement, repair, and healing of his femoral neck fracture on imaging and clinical evaluation. He gradually returned to activity with the assistance of physical therapy and was recommended to avoid situations where he might be at high risk for bony trauma. He progressed towards running, yet has continued to use stationary bicycling as his main source of cardiovascular fitness due to fear of fracture with repetitive weight bearing activities.

Author's Comments:
Subclinical hypergonadotropic hypogonadism is likely secondary to an unknown primary testicular failure, in this case, possibly a long-standing varicocele.

There has been recent guidance for testosterone replacement in patients with hypogonadism such as Klinefelter Syndrome, even in a subclinical hypogonadism state. Goal replacement testosterone doses in this population are based off of bivariate charts of testosterone versus luteinizing hormone (LH) levels with the goal of preventing osteoporosis, improving muscle mass, energy levels, sexual function, as well as other mood symptoms. These studies are paving the way for discussions regarding management decisions in young hypogonadal populations, especially subclinical hypogonadal patient populations where testosterone measurements alone tend to underestimate the prevalence of testicular failure.

This case also highlights the need to identify and treat vitamin D deficiency in known osteoporotic causes but also to continue to dig deeper to ensure no additional risk factors are identified.

Editor's Comments:
Osteoporosis is clinically diagnosed in the presence of a fragility fracture or a bone mineral density measurement by DEXA with a T-score equal to, or less than -2.5 standard deviations. The T-score compares the patient's bone mineral density with that of a young adult reference range. On the other hand, a Z-score compares the patient's bone mineral density to an age-matched population. Z-scores are not used for diagnosing osteoporosis, however a score of -2 or lower is considered "low bone mass".
Two major causes of secondary osteoporosis in men are hypogonadism and vitamin D deficiency, however it is important to complete a thorough evaluation to consider other endocrine/metabolic diseases, nutritional conditions, and potential medications. Furthermore, secondary and subclinical hypogonadism in men have been associated with vitamin D deficiency. Hypogonadism in men treated with testosterone replacement therapy, however evidence is lacking to support testosterone replacement therapy in subclinical or compensated hypogonadism in men.

References:
1. Diab DL, Watts NB. Updates on Osteoporosis in Men. Endocrinology and metabolism clinics of North America. 2021;50(2):239-249.
2. Lee DM, Tajar A, Pye SR, et al. Association of hypogonadism with vitamin D status: the European Male Ageing Study. Eur J Endocrinol. 2012;166(1):77-85.
3. Giannetta E, Gianfrilli D, Barbagallo F, Isidori AM, Lenzi A. Subclinical male hypogonadism. Best Pract Res Clin Endocrinol Metab. 2012;26(4):539-550.

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