M.I.V, a 34-year-old male, was born at normal gestation age with normal weight. Since the age of 2, he has suffered 48 bone fractures located at lower and upper limbs, vertebrae and ribs, all of which healed with good callus formation.
Dentinogenesis imperfecta and/or taurodontism, blue sclerae and hypermobile joints appeared in early childhood. Puberty started at 16 years of age and was delayed and incomplete. Clinical examination revealed: current height 175 cm, weight 67 kg, eunuchoid proportions of the skeleton without deformities, thin and easily bruised skin, poor hairiness on the face, absence of hair on the trunk and extremities and male type of pubic and axillary hair. The sclerae were moderately blue and most of the teeth were not intact. The genital status revealed penile-testicular dissociation: penile length 7 cm, testicular volume on each side 2 ml, firm. Gynecomastia, hearing loss and cardiovascular or other visceral abnormalities were absent. The laboratory analysis revealed: serum osteocalcin 50.2 ng/mL (range 3.4-9.1 ng/mL), urine hydroxyproline 40 mM/mM, creatinine (range 2.43-19.25) and follicle-stimulating hormone (FSH) 20.7 nmol/L (range 1.7-3.5), normal levels of serum calcium and phosphorus and in 24-hour urine samples, of total and bone fraction of alkaline phos­phatase and of glucosoaminoglycan excretion, C-terminal propeptide of collagen type I-94 nM/mL (range 76-163), LH-12, 8 nmol/L (range 4.0-18.0), serum testosterone 22 nmol/L (range:8.2-34.6) and sex hormone binding globulin (SHBG) 50 nmol/L (range 15-70). The radiological examination of the skeleton revealed a severe, diffuse osteoporosis, decreased bone density, generalized rarefaction of trabecular structure, thin cortex of long bones, asthenic thorax, marked demineralization of the ribs, thin cortices of the clavices, distinctly osteoporotic spine with vertebral deformities, anterior wedging and biconcave appearance of the vertebral bodies, especially the mid and lower thoracic and upper lumbar vertebrae. The pelvic bones were osteoporotic, the trabeculae were thinned or lost, particularly in the acetabular region. The lateral radiography of the skull demonstrated thinning of the inner and outer tables of calvarium, moderately decreased density of the frontal, parietal and occipital bones, and osteoporosis of the sella turcica. The previous fractures of long bones were well healed with normal callus formation. Osteodensitometry (DEXA-Norland) of left forearm showed a severe osteoporosis with a high fracture risk: T-score 2.89, Z-score 2.87 (Dist. R+U), T-score 2.61, Z-score 2.48 (Prox. R+U). A testicular ejaculate revealed azoospermia. Cytogenetic analysis showed a 47 XXY karyotype in all lymphocyte metaphases.
The family study revealed an autosomal dominant mode of inheritance of a mild-to-moderate form of OI. The mother of the proband, her brother, his son and the grandfather were affected. The second female child of his uncle was healthy and had two healthy children. The affected cousin married a female with OI whose pregnancy was aborted and showed multiple intrauterine fractures in the fetus. All affected members had a current height of not more than 165 cm, without apparent deformities, with fewer fractures (up to 24), moderate joint hypermobility, no hearing loss but blue sclerae. The patient was treated with biphosphonate [10 mg daily Fosamax, (MSD)] to inhibit the osteoclastic bone resorption, hormone replacement therapy with testosterone (Sustanone 250 mg i.m./20 days) and physical therapy. For the past 3 years, there have been no new fractures while on this treatment regimen.