Single-Dose Pharmacokinetics and Tolerability of Alendronate 35- and 70-Milligram Tablets in Children and Adolescents with Osteogenesis Imperfecta Type I

Ward, Leanne M.; Denker, Andrew E.; Porras, Arturo G.; Shugarts, Sarah; Kline, Walter F.; Travers, Rose; Mao, Chien-Lin; Rauch, Frank; Maes, Andrea; Larson, Patrick; Deutsch, Paul; Glorieux, F. H.

doi:10.1210/jc.2004-2054

Cited by 56 publications

(35 citation statements)

References 26 publications

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“…A pharmacokinetics study of oral, weekly alendronate in children with mild OI recently showed that the absorption was <1%, comparable to adult studies [98], and that there were documented side effects similar to the acute phase reaction observed with intravenous pamidronate. Alpadronate, administered as weekly tablets to children with severe OI, was shown to positively impact on bone mass, density, and fracture rates, although reshaping of compressed vertebrae and mobility were unchanged after 2 years’ treatment in this randomized, controlled trial of 34 patients [99].…”

Section: Approach To Diagnosis and Treatmentmentioning

confidence: 68%

Osteoporosis due to Glucocorticoid Use in Children with Chronic Illness

Ward

2005

Horm Res Paediatr

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Osteoporosis is increasingly recognized as a complication of chronic childhood illnesses, particularly when glucocorticoids (GCs) are necessary for treatment. Elucidation of the mechanisms leading to bone fragility in these settings requires disentanglement of the relative contributions of myriad risk factors, including disease activity, muscle weakness, immobilization, delayed growth and puberty, compromised nutrition, and osteotoxic medications. Over the years, bone mass and density evaluations by dual energy X-ray absorptiometry (DXA) have become popular for assessing bone health in children; however, such measurements are difficult to interpret because of the confounding effect of bone size and the lack of DXA-based densitometric criteria for defining osteoporosis in childhood. Recently, a new diagnostic approach for evaluation of densitometric data in children has been suggested, driven by Frost’s mechanostat theory. A diagnostic algorithm based on the mechanostat theory of bone-muscle development is proposed for the characterization of bone disease in children with chronic illness. In addition to DXA-based assessments, techniques such as peripheral quantitative computerized tomography and ilial histomorphometry, for which there are pediatric reference data, are gaining ground in the characterization of skeletal changes due to chronic illness. Although these diagnostic techniques expand our understanding of osteoporosis in children, they do not replace clinical assessment. Concrete clinical evidence for GC-induced bone fragility can be seen in spinal changes due to vertebral compression, with spinal morphometry emerging as an essential, but frequently overlooked, tool in the evaluation of children’s bone health. Presently, osteoporosis treatment in the chronic illness setting remains experimental and should be restricted to clinical studies. Following an understanding of the natural history of GC-induced osteoporosis in children, randomized, placebo-controlled prevention and intervention trials will be the next step toward the development of clinical practice guidelines.

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Section: Approach To Diagnosis and Treatmentmentioning

confidence: 68%

Osteoporosis due to Glucocorticoid Use in Children with Chronic Illness

Ward

2005

Horm Res Paediatr

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“…To provide equivalent oral and intravenous doses, it was assumed based on available in vitro and in vivo data that the oral alendronate dose had 0.5% intestinal absorption, (20) 50% skeletal bioavailability, (21) and five times greater potency than intravenous pamidronate. (22) Thus, daily oral alendronate over 4 months was considered to be equivalent to intravenous pamidronate given over 3 consecutive days, every 120 days.…”

Section: Methodsmentioning

confidence: 99%

Two-Year Clinical Trial of Oral Alendronate Versus Intravenous Pamidronate in Children With Osteogenesis Imperfecta

DiMeglio

Peacock

2006

Journal of Bone and Mineral Research

114

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A 2-year prospective, partially randomized open-label trial comparing oral alendronate with intravenous pamidronate therapy in children with OI showed equivalence in increasing total body BMD, spine BMD, and linear growth, and decreasing bone turnover and fracture incidence. Children with mild OI had greater responses than severe OI in BMD and growth.Introduction: Bisphosphonate therapies increase BMD and may reduce fractures in children with osteogenesis imperfecta (OI). A study directly comparing oral with intravenous bisphosphonate has not been published. This clinical trial compares oral alendronate with intravenous pamidronate in children with OI using an open-label, prospective, 2-year, randomized design. Materials and Methods: Children over the age of 3 years were stratified by bone age, pubertal stage, and type of OI and then randomized to receive oral alendronate 1 mg/kg/day in tablet form or intravenous pamidronate, 3 mg/kg/4 months. One child was assigned to pamidronate. One child randomized to intravenous pamidronate changed to oral alendronate. Eighteen children completed 12 months of therapy: nine on oral alendronate and nine on intravenous pamidronate. Primary outcome efficacy was increase in BMD. Secondary outcomes included changes in bone turnover biomarkers, fracture incidence, and growth. Results: Total body and lumbar spine BMD increased, turnover markers decreased, and linear growth increased equivalently with oral and intravenous therapy. Fracture incidence showed a trend to decrease in both groups, with a significant decrease in fracture rates when the oral and intravenous groups were pooled. There were greater responses in BMD and growth in children with milder OI (type I) than those with more severe disease (types III and IV), but there were no significant effects of age or pubertal stage. Conclusions: Oral and intravenous bisphosphonate therapies are equally effective in children with OI and are particularly effective in milder forms. The oral route is highly acceptable in children and has practical advantages over the intravenous route.

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“…Adverse effects of bisphosphonates are few and minor in this population (gastrointestinal complaints, fever, headache, small decreases in lymphocyte counts). 54,59,60 Flu-like symptoms described as "acute phase reactions" are common with IV administration of bisphosphonates with the first infusion. 54,59 The results presented in the Cochrane review provide evidence, albeit in a relatively small population, of significant improvement in BMD in individuals with OI when treated with either oral or IV bisphosphonates.…”

Section: Bisphosphonate Therapymentioning

confidence: 99%

Osteogenesis imperfecta: Recent findings shed new light on this once well-understood condition

Basel

Steiner

2009

Genetics in Medicine

149

118

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Single-Dose Pharmacokinetics and Tolerability of Alendronate 35- and 70-Milligram Tablets in Children and Adolescents with Osteogenesis Imperfecta Type I

Abstract: The mean oral bioavailability of 35- and 70-mg ALN tablets was less than 0.6%, comparable to adult studies. Adverse experiences from single-dose ALN were minor, and the drug was generally well-tolerated.

Cited by 56 publications

References 26 publications

Osteoporosis due to Glucocorticoid Use in Children with Chronic Illness

Osteoporosis due to Glucocorticoid Use in Children with Chronic Illness

Two-Year Clinical Trial of Oral Alendronate Versus Intravenous Pamidronate in Children With Osteogenesis Imperfecta

Osteogenesis imperfecta: Recent findings shed new light on this once well-understood condition

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