Efficacy of Denosumab for Osteoporosis in Three Female Patients with Osteogenesis Imperfecta

Efficacy of Denosumab for Osteoporosis in Three Female Patients with Osteogenesis Imperfecta

MASASHI UEHARA,¹ YUKIO NAKAMURA,¹ JUN TAKAHASHI,¹ MIKIO KAMIMURA,² SHOTA IKEGAMI,¹ TAKAKO SUZUKI,¹ SHIGEHARU UCHIYAMA,^1,3 TOMOMI YAMAGUCHI,⁴ TOMOKI KOSHO⁴ and HIROYUKI KATO¹

¹Department of Orthopaedic Surgery, Shinshu University School of Medicine, Matsumoto, Nagano, Japan
²Center of Osteoporosis and Spinal Disorders, Kamimura Orthopedic Clinic, Matsumoto, Nagano, Japan
³Department of Orthopaedic Surgery, Okaya City Hospital, Okaya, Nagano, Japan
⁴Department of Medical Genetics,ShinshuUniversity School of Medicine, Matsumoto, Nagano, Japan

Osteogenesis imperfecta (OI) is an inherited bone disorder that causes fractures due to impaired production of collagen type I. In recent years, denosumab, a human monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), has become widely used as an anti-osteoclastic agent for osteoporosis. This study investigated osteoporotic cases of OI to examine effects of denosumab on bone fragility. This was a retrospective, consecutive case series that included 3 female patients aged 42, 40, and 14 years, respectively. One patient carries a point mutation (c.G769A) in the COL1A1 gene, encoding collagen type I alpha 1 chain, which causes an amino-acid substitution (p.G257R). By contrast, no mutation was found in the analyzed regions of the OI responsive genes in another two patients (mother and daughter). These three patients underwent subcutaneous injection of denosumab every 6 months. All patients underwent dual-energy X-ray absorptiometry for bone mineral density (BMD) measurement of the lumbar 1-4 spine (L-BMD) and bilateral hips (H-BMD) before and during treatment. BMD and laboratory data were evaluated before, between 2 and 4 months, and at 6, 12, 18, and 24 months of therapy. No fractures or severe side effects, such as hypocalcemia, were observed during denosumab treatment. Both L-BMD and H-BMD were increased by denosumab. At 24 months, the mean percentage changes in L-BMD and H-BMD were 14.7% and 15.1%, respectively. In conclusion, no bone fragility fractures occurred during 2 years of denosumab administration in OI patients. Denosumab therefore is a good therapeutic option in the OI patients.

keywords —— bone mineral density; bone turnover marker; denosumab; fracture; osteogenesis imperfecta

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Tohoku J. Exp. Med., 2017, 242, 115-120

Correspondence: Yukio Nakamura, M.D., Ph.D., Department of Orthopaedic Surgery, Shinshu University School of Medicine, Asahi 3-1-1, Matsumoto, Nagano 390-8621, Japan.

e-mail: yxn14@aol.jp