Bisphosphonate treatment in ochronotic osteoporotic patients.

In ochronotic patients, abnormalities in bone metabolism leading to increased bone loss have been reported. Therefore, we attempted antiresorptive therapy to (almost) partially reverse bone loss in four out of five osteopenic or osteoporotic ochronotic patients, two men and two women, aged 56-82 years. Each patient was treated with a 70-mg tablet of alendronate weekly and 1,000 mg/day of elemental calcium, such as gluconolactate or carbonate, throughout 24 months. Before starting therapy, and after 1 and 2 years of treatment, the bone mineral density (BMD) at the femoral subregions and at the lumbar spine was measured (in grams per square centimeter and as a T score) by dual energy X-ray absorptiometry. A 50-year-old osteopenic ochronotic man refusing the treatment underwent the same checks. The BMD was measured in all patients on the same densitometer by the same operator. The results showed a progressive decrease of the femoral subregion BMD measurements both in the bisphosphonate-treated patients and in the untreated patient. In particular, the percentage differences with respect to the basal values of the total femur BMD measurements ranged from -0.52 to -6.72% in the first year and from -5.29 to -9.05% in the second year. The lumbar spine BMD measurements provided spuriously overestimated results. Moreover, two treated patients and the untreated patient experienced fragility fractures of the femur. The study showed that osteoporosis and fragility fractures are prominent manifestations in the natural history of ochronosis. Matrix microdamage, osteocyte viability, and collagen cross-linking impairment, due to homogentisic acid and to its polymer, might be the processes involved. For this reason, the bisphosphonate therapy was ineffective.