Eleven years of experience with bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I

Abstract

We report the 11-year follow-up of a man with osteogenesis imperfecta type I who was treated with bisphosphonates and alfacalcidol. A 36-year-old Japanese man with osteogenesis imperfecta type I who had frequently experienced painful fragility fractures consulted our clinic because of chronic back pain. The patient had multiple morphometric vertebral fractures and a low bone mineral density (BMD) at the lumbar spine. The patient was treated with cyclical etidronate 200 mg, for 2 weeks every 3 months, plus alfacalcidol 1 μg daily, for 2 years; and alendronate 5 mg daily or 35 mg weekly, plus alfacalcidol 1 μg daily for 9 years. After 11 years of treatment, BMD at the lumbar spine increased by 6.4%, following a 20.3% reduction in serum alkaline phosphatase. Serum calcium, phosphorus, and intact parathyroid hormone levels remained within the normal ranges. Three clinical fractures occurred at two ribs and the metacarpus, and two morphometric vertebral fractures occurred at the thoracic spine during the 11-year treatment period, but the patient experienced no adverse effects. Thus, the present case report shows the long-term outcome and safety of bisphosphonate plus alfacalcidol treatment in a man with osteogenesis imperfecta type I.

Keywords: alendronate; bone mineral density; etidronate; fragility fracture; osteogenesis imperfecta.

Figure 1

Radiographs of thoracic and lumbar spine. Notes: Lateral views before treatment. Radiographs of thoracic and lumbar spine before treatment showed the existence of morphometric vertebral fractures at the 6th, 8th, and 10th thoracic vertebrae and the 2nd lumbar vertebra. Abbreviation: T12, 12th thoracic spine.

Figure 2

Changes in lumbar spine BMD during the 11-year period of treatment. Notes: Treatment with cyclical etidronate plus alfacalcidol was initiated. The lumbar spine BMD increased at one year after the start of etidronate plus alfacalcidol treatment but decreased at 2 years. Treatment was switched from etidronate plus alfacalcidol to alendronate plus alfacalcidol, and this treatment was continued for 9 years. The increase in lumbar spine BMD from baseline was 2.8% at one year, 2.1% at 2 years, 4.6% at 3 years, 4.6% at 4 years, 5.0% at 5 years, 5.0% at 6 years, 5.3% at 7 years, 5.9% at 8 years, 6.4% at 9 years, 6.2% at 10 years, and 6.4% at 11 years. Abbreviations: BMD, bone mineral density; ETD, etidronate; ALN, alendronate.

Figure 3

Changes in biochemical markers during the 11-year period of treatment. Notes: The patient was treated with cyclical etidronate plus alfacalcidol for 2 years and alendronate plus alfacalcidol for 9 years. The serum alkaline phosphatase level decreased at one and 2 years after the start of etidronate plus alfacalcidol treatment and was sustained thereafter for 9 years. The reduction in the serum alkaline phosphatase level was 16.2% at one year, 24.2% at 2 years, 23.7% at 3 years, 26.5% at 4 years, 26.7% at 5 years, 24.2% at 6 years, 20.6% at 7 years, 21.2% at 8 years, 21.7% at 9 years, 21.2% at 10 years, and 20.3% at 11 years. The serum calcium, phosphorus, and intact parathyroid hormone levels stayed within the normal ranges during the 11-year period of treatment. A: Calcium, B: Phosphorus, C: ALP, D: intact PTH. Abbreviations: ALP, alkaline phosphatase; PTH, parathyroid hormone; ETD, etidronate; ALN, alendronate.

Figure 4

Radiographs of thoracic and lumbar spine. Notes: Lateral views after 11 years of treatment. After 11 years of treatment, radiographs of the thoracic and lumbar spine revealed the existence of morphometric vertebral fractures (at the 5th, 6th, 8th, 9th, and 10th thoracic vertebrae and the 2nd lumbar vertebra), suggesting the occurrence of new morphometric vertebral fractures (at the 5th and 9th thoracic vertebrae). Abbreviation: T12, 12th thoracic spine.