A 65-year-old male patient diagnosed with OI following a study of a daughter who was also affected. He had no previous family history of the disease.

He reported a history of several fractures (approximately 6-7) during childhood and adolescence following minimal trauma, the first of the humerus at the age of 2 years. During adulthood he had had two new fractures in the elbow and shoulder. All had been treated conservatively. He received calcium treatment during childhood. He had also had multiple sprains and several muscle ruptures throughout his life. Diagnosed with otosclerosis, he had undergone surgery for stapedectomy of both ears.

He was referred to our clinic for osteoporosis detected in bone densitometry (DXA), which showed T-scores of -3.4 in the lumbar spine (L1-L4), -3 in the femoral neck and -2.8 in the total femur. He was asymptomatic.

Physical examination revealed a height of 162 cm, blue sclerae and the presence of dentinogenesis imperfecta. There were no thoracic deformities, nor in the dorsolumbar spine or limbs, except for the right elbow (postfracture). No hyperlaxity was observed.

The calcium-phosphorus metabolism study showed normal levels of calcium, phosphorus, calciuria, and parathormone (iPTH). 25-hydroxyvitamin D (25OHCC) levels were in the range of insufficiency: 22 ng/ml (desirable values >30 ng/ml). Bone remodelling markers were in the normal range. Other endocrine causes of osteoporosis were ruled out.

As part of our protocol for the study of patients with OI, a cervical spine X-ray ruled out basilar impression, and a chest X-ray showed degenerative changes in the spine; the echocardiogram showed minimal dilatation of the ascending aorta; respiratory function tests were normal, and the abdominal ultrasound ruled out renal lithiasis.

A genetic study was performed by massive sequencing by NGS (Next-Generation Sequencing) of the COL1A1, COL1A2, CRTAP and LEPRE1 genes, detecting a heterozygous deletion of a Guanine (c.3524delG) in the COL1A1 gene. This mutation results in a change in the reading pattern, which, at the level of the collagen protein, causes a premature stop codon (p.Gly1175Valfs*64) and is therefore likely to be a pathogenic change. Other changes were detected and considered polymorphisms.

Treatment with weekly alendronate associated with daily calcium and vitamin D supplements was recommended, showing a discrete densitometric improvement after 1 year of treatment (T-scores of -3.2 in the lumbar spine, -2.9 in the femoral neck and -2.4 in the total femur).