Pamidronate treatment stimulates the onset of recovery phase reducing fracture rate and skeletal deformities in patients with idiopathic juvenile osteoporosis: comparison with untreated patients

Abstract

Although spontaneous remission occurs in patients with idiopathic juvenile osteoporosis (IJO), permanent bone deformities may occur. The effects of long-term pamidronate treatment on clinical findings, bone mineral status, and fracture rate were evaluated. Nine patients (age 9.8 ± 1.1 years, 7 males) with IJO were randomized to intravenous pamidronate (0.8 ± 0.1 mg/kg per day for 3 days; cycles per year 2.0 ± 0.1; duration 7.3 ± 1.1 years; n = 5) or no treatment (n = 4). Fracture rate, phalangeal quantitative ultrasound, and lumbar bone mineral density (BMD) by dual energy X-ray absorptiometry at entry and during follow-up (range 6.3-9.4 years) were assessed. Bone pain improved in treated patients. Difficulty walking continued for 3-5 years in untreated patients, and vertebral collapses occurred in three of them. During follow-up, phalangeal amplitude-dependent speed of sound (AD-SoS), bone transmission time (BTT), and lumbar BMDarea and BMDvolume progressively increased in treated patients (P < 0.05-P < 0.0001). In untreated patients AD-SoS and BTT decreased during the first 2-4 years of follow-up (P < 0.05-P < 0.01); lumbar BMDarea increased after 6 years (P < 0.001) whereas BTT and lumbar BMDvolume increased after 7 years of follow-up (P < 0.05 and P < 0.001, respectively). At the end of follow-up, AD-SoS, BTT, lumbar BMDarea, and BMDvolume Z-scores were lower in untreated patients than in treated patients (-2.2 ± 0.3 and -0.5 ± 0.2; -1.9 ± 0.2 and -0.6 ± 0.2; -2.3 ± 0.3 and -0.7 ± 0.3; -2.4 ± 0.2 and -0.7 ± 0.3, P < 0.0001, respectively). Fracture rate was higher in untreated patients than in treated patients during the first 3 years of follow-up (P < 0.02). Our study showed that spontaneous recovery of bone mineral status is unsatisfactory in patients with IJO. Pamidronate treatment stimulated the onset of recovery phase reducing fracture rate and permanent disabilities without evidence of side-effects.

Biochemical markers of bone turnover in children with clinical bone fragility

“…Many studies have demonstrated beneficial outcomes with pamidronate treatment in children with OI [1][2][3], as well as other bone fragility conditions such as idiopathic juvenile osteoporosis [4], spastic quardriplegic cerebral palsy [5][6][7], neuromuscular disorders [8], steroids-induced osteoporosis [9], and fibrous dysplasia [10]. Bisphosphonates decrease bone turnover by decreasing bone resorption.…”

The Use of Bisphosphonates in Pediatrics

“…In patients with osteogenesis imperfecta, improved or no effect on linear growth is reported [84]. In patients with IJO, a normal pattern of linear growth during long-term intravenous pamidronate treatment was found [5]. …”

“…A schematic representation of bisphosphonate effects on bone cells is depicted in figure 2. The positive effect of bisphosphonates on bone formation, even in the face of reduced overall bone remodeling, could explain part of the antifracture efficacy and bone mass recovery in patients with idiopathic juvenile osteoporosis (IJO) during pamidronate treatment [5]. Table 1 shows the chemical structure, route of administration, dose range, and potency relative to etidronate of the main bisphosphonates used in pediatric patients.…”

“…Although there is no reliable treatment in patients with IJO, bisphosphonates would seem to be the most effective therapy for improving painful symptoms and bone mass accumulation [17]. A study showed that intravenous pamidronate stimulated the onset of recovery phase, improving bone mineral status, reducing fracture rate and preventing skeletal deformities [5]. …”

“…In order to reduce the risk of hypocalcemia the patients could receive an intravenous 10% calcium gluconate infusion after each bisphosphonate intravenous infusion [5]. Although there are no official recommendations, some clinical, biochemical and imaging assessments may be suggested in pediatric patients receiving bisphosphonate therapy (table 5).…”