Osteogenesis imperfecta: Anthropometric, skeletal and mineral metabolic effects of long-term intravenous pamidronate therapy

Vallo, Alfredo; Rodriguez-Leyva, Francisco; Soriano, Juan Rodríguez

doi:10.1080/08035250500434785

Cited by 17 publications

(7 citation statements)

References 31 publications

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“…Nevertheless, our results are in line with other studies showing that bisphosphonates would be safe with regard to growth in OI children [6,24,26,27,28,29]. However, most of our patients have not yet reached final height, and thus it is not possible to conclude whether the growth improvement during the first years of pamidronate treatment reported here will also translate into an increased adult height.…”

Section: Discussionsupporting

confidence: 83%

Intravenous Pamidronate Treatment Improves Growth in Prepubertal Osteogenesis Imperfecta Patients

Heino¹,

Albrecht²,

Laurenčikas³

et al. 2011

Horm Res Paediatr

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Background/Aims: Pamidronate is widely used to treat pediatric patients with osteogenesis imperfecta (OI). We aimed at delineating the effects of monthly pamidronate therapy on the growth of different body segments in prepubertal OI patients. Methods: The study included 14 prepubertal patients (12 boys, 2 girls) with mild forms of OI (type I and IV). The mean age at treatment start was 7:8 years:months (3:7–11:0). Pamidronate was given as monthly intravenous infusions. The patients were measured 1 year before, at treatment start and 1 and 2 years after treatment start. Results: Height standard deviation score (SDS) and sitting height SDS significantly increased (p < 0.05) during the first year of treatment when compared to the pre-treatment year. No further improvement was detected during the second year of treatment. However, when plotted on disease-specific growth charts (untreated patients with the same OI types), height gain was significant during the first (p < 0.001) and second (p < 0.05) years of treatment. All patients increased their bone mineral density throughout the follow-up. Conclusion: Monthly pamidronate improves the growth of prepubertal patients with mild OI, where the most prominent growth stimulation is seen in the upper body segment.

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Section: Discussionsupporting

confidence: 83%

Intravenous Pamidronate Treatment Improves Growth in Prepubertal Osteogenesis Imperfecta Patients

Heino¹,

Albrecht²,

Laurenčikas³

et al. 2011

Horm Res Paediatr

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“…Also in 2006, Vallo et al

^{(^{(46)})}

showed that PMD therapy for pediatric OI led to “size‐adjusted” spine BMD increments that stabilized or sometimes waned after 2 yr of treatment. They questioned whether repeated cycles of PMD were necessary or would courses without intermediate therapy be of identical benefit.…”

Section: Discussionmentioning

confidence: 99%

“…With the exception of the 1992 paper by Van Persijn van Meerten et al,

^{(^{(34)})}

no mention is made in these publications

^{(^{(37,41,43,45,46)})}

of metaphyseal mineral content or shaping after BP withdrawal, because treatment was continuing or finishing.…”

Section: Discussionmentioning

confidence: 99%

Bisphosphonate-Induced Osteopetrosis: Novel Bone Modeling Defects, Metaphyseal Osteopenia, and Osteosclerosis Fractures After Drug Exposure Ceases

Whyte

McAlister

Novack

et al. 2008

Journal of Bone and Mineral Research

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ABSTRACT:In 2003, we reported on a 12-yr-old boy who had developed osteopetrosis (OPT) while receiving pamidronate (PMD) for idiopathic bone pain and enigmatic elevation in circulating bone alkaline phosphatase. Now 17 yr of age, he was re-evaluated 6.5 yr after PMD exposure stopped. Our patient described less bone pain but further limb fractures. His growth plates were fused, yet hyperphosphatasemia persisted. Radiographs documented interval fractures of a metacarpal, an osteosclerotic distal radius, and a dense diaphyseal segment of an ulna where a "chalkstick" break remained incompletely healed after 2 yr. There was new L 4 spondylolysis, and previous L 5 spondylolysis had caused spondylolisthesis. Modeling disturbances of OPT persisted, but partial recovery was shown by metaphyseal surfaces with a unique concave shape. Metaphyseal osteosclerosis had remodeled imperfectly to become focal areas of dense, diaphyseal bone. Newer metaphyseal bone was unexpectedly osteopenic, especially in his distal femurs where cortices were thin and a paucity of trabeculae was documented by CT. Femoral necks had become short and wide with an abnormal contour. A "bone-within-bone" configuration was now present throughout his skeleton. In vertebrae, endplates were thin, and trabecular osteopenia was present central and peripheral to the bands of osteosclerosis. BMD Z-scores assessed by DXA had decreased into the normal range in his spine, hip, and whole body. Iliac crest biopsy showed active bone formation, with much less accumulated primary spongiosa than during the PMD infusions. Osteoclasts that had been dysmorphic, round cells without polarization and off of bone surfaces were now unremarkable in number, location, and appearance. In conclusion, bisphosphonate toxicity during childhood can impair skeletal modeling and remodeling with structural changes that evolve and carry into adult life.

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“…Bisphosphonates are currently the mainstay of treatment and the different treatment modalities include cyclic infusions of pamidronate and neridronate, as well as oral treatment with alendronate (ALN) [2–6]. Bisphosphonates, which inhibit osteoclast activity, have been shown to ease chronic bone pain, increase bone mineral density and strength, reduce fractures, and improve final height probably due to a decreased incidence of vertebral fractures [4, 7, 8]. However, limitations in bisphosphonate therapy remain, including occasional respiratory distress with the first infusion [9].…”

Section: Introductionmentioning

confidence: 99%

RANKL Inhibition Improves Bone Properties in a Mouse Model of Osteogenesis Imperfecta

Bargman¹,

Huang²,

Boskey³

et al. 2010

Connective Tissue Research

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Recently, a new class of agents targeting the receptor activator of nuclear factor-κB ligand (RANKL) pathway has been developed for the treatment of osteoporosis and other bone diseases. In the current study, inhibition of the RANKL pathway was evaluated to assess effects on "bone quality" and fracture incidence in an animal model of osteogenesis imperfect (OI), the oim/oim mouse. Juvenile oim/oim (~6 weeks old) and wildtype (+/+) mice were treated with either a RANKL inhibitor (RANKFc) or saline. After treatment, bone density increased significantly in the femurs of both genotypes. Femoral length decreased with RANK-Fc in +/+ mice. Geometric measurements at mid-diaphysis in the oim/oim groups showed increases in the ML periosteal and endosteal diameters and AP cortical thickness in the treated groups. Within +/+ groups, ML cortical thickness and ML femoral periosteal diameter were significantly increased with RANK-Fc. Biomechanical testing revealed increased stiffness in oim/oim and +/+ mice. Total strain was increased with treatment in the +/+ mice. Histologically, RANKL inhibition resulted in retained growth plate cartilage in both genotypes. The average number of fractures sustained by RANK-Fc-treated oim/oim mice was not significantly decreased compared to saline treated oim/oim mice. This preclinical study demonstrated that RANKL inhibition at the current dose improved density and some geometric and biomechanical properties of oim/oim bone, but it did not decrease fracture incidence. Further studies that address commencement of therapy at earlier time points are needed to determine whether this mode of therapy will be clinically useful in OI.

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Osteogenesis imperfecta: Anthropometric, skeletal and mineral metabolic effects of long-term intravenous pamidronate therapy

Abstract: Our results confirm that cyclical pamidronate infusions reduce the incidence of bone fractures and allow normal growth. The improvement in bone mass initially observed after the first 2 y of therapy is not always sustained over the following years despite maintenance of therapy.

Cited by 17 publications

References 31 publications

Intravenous Pamidronate Treatment Improves Growth in Prepubertal Osteogenesis Imperfecta Patients

Intravenous Pamidronate Treatment Improves Growth in Prepubertal Osteogenesis Imperfecta Patients

Bisphosphonate-Induced Osteopetrosis: Novel Bone Modeling Defects, Metaphyseal Osteopenia, and Osteosclerosis Fractures After Drug Exposure Ceases

RANKL Inhibition Improves Bone Properties in a Mouse Model of Osteogenesis Imperfecta

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