Endocrine Abstracts

Context: It is mandatory to rule out secondary causes of osteoporosis in young adult males presenting with osteoporotic fractures. If no such causes are identified, it is important to remember that an underlying genetic defect might explain the phenotype. This has implications for treatment, follow-up, as well as screening of family members.

Case: A 40-year old male (172 cm, 78 kg) with a past medical history of asthma and pollen allergies, initially presented to the orthopedic department with painful right groin. The pain had started 10 days after he fell on his back at work. The pain was provoked by weight-bearing and spread to both groins 1 month after the initial presentation - which on examination was pain on rotation of both hip joints. After the initial non-diagnostic pelvic radiograph and ultrasound, pelvic MRI showed bilateral stress fractures of the femoral necks. Previous history of fractures included high-energy fractures of right thumb and right fifth finger. The patient had a family history of osteoporosis (father and sister) and his father had had a femoral neck fracture at the age of 60. There was no history of fractures from the maternal side. On a DEXA scan, bone mineral density was osteopenic at the lumbar spine and right femoral neck and osteoporotic at the left femoral neck with a T score of −2.8. Primary hyperparathyroidism, and coelic disease were excluded. Serum 25-hydroxyvitamin D(3) was low at 33 nmol/L (reference range > 40). Iliac crest bone biopsy showed low trabecular bone volume with a normal turnover rate, normal osteoblast and osteoclast surfaces, normal mineralising surface, but with a slightly low mineral apposition. Bone biopsy findings were consistent with normal-turnover osteoporosis. The patient was treated with calcium and vitamin D supplementation and alendronate for two years. The bilateral femoral neck fractures healed with conservative treatment but the patient continues to have bilateral hip pains and has early arthrosis of the left hip. Evaluation in Endocrine Department showed no features of Cushing’s disease. Both hypercortisolism and hypogonadism were biochemically ruled out. However, genetic analysis revealed a novel mutation in TMEM38B, which to our knowledge is the first report of this specific mutation, which causes osteogenesis imperfecta type XIV.

Discussion: Genetic defects may underlie not only pediatric but also adult-onset fragility osteoporosis. Here, we report a novel mutation in TMEM38B causing type XIV osteogenesis imperfecta and bilateral femoral stress fractures in an adult male.