Chronic idiopathic hyperphosphatasia: normalization of bone turnover with cyclical intravenous pamidronate therapy

Chronic idiopathic hyperphosphatasia (CIH), or juvenile Paget disease, is a rare disorder characterized by increased bone turnover and progressive enlargement of bones. We report a girl, 6 1/2 years old, with a history of three fractures, short stature, delayed eruption of teeth, and poor hair growth. She had a waddling gait, bone deformities, kyphoscoliosis, hyperlordosis, genu valgum and curvature of her limbs. She also had progressive hearing loss but other cranial nerves were unaffected. Laboratory studies indicated high bone turnover: serum alkaline phosphatase: 4047 IU/l (normal value: 150-550), urinary hydroxyproline: 1205 mg/g creatinine (n.v.: 60-160), and urinary CrossLaps: 4360 microg/mmol creatinine (n.v.: 450-2100). Radiographs demonstrated generalized skeletal involvement with osteoectasia (expansion) of long bones, diffuse sclerosis, cotton wool appearance of the skull, absence of mastoid pneumatization, and crushed dorsal and lumbar vertebrae. Iliac crest biopsy was compatible with CIH. Cyclical intravenous pamidronate (1 mg/kg/day during 3 h, 3 consecutive days at 2- to 3-month intervals) was administered during 2 years with oral calcium 500 mg and vitamin D 1000 IU/day. Oral pamidronate was added after 11 months of i.v. therapy. Treatment-induced remarkable clinical and radiographic improvement with normalization of bone markers of osteoblastic and osteoclastic activity, including bone alkaline phosphatase, urinary hydroxyproline, and urinary CrossLaps.