Alendronate for the Treatment of Pediatric Osteogenesis Imperfecta: A Randomized Placebo-Controlled Study

Ward, Leanne M.; Rauch, Frank; Whyte, Michael P.; D’Astous, Jacques; Gates, Phillip E.; Grogan, Dennis P.; Lester, Edward L.; McCall, Richard E.; Pressly, Thomas A.; Sanders, James O.; Smith, Peter A.; Steiner, Robert D.; Sullivan, Elroy; Tyerman, Gayle H.; Smith-Wright, D. L.; Verbruggen, Nadia; Heyden, Norman; Lombardi, Antonio; Glorieux, Francis H.

doi:10.1210/jc.2010-0636

Cited by 191 publications

(189 citation statements)

References 37 publications

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“…The required size of the study population was calculated on the hypothesis that supplementation with oral vitamin D 3 would render lumbar spine areal BMD z-score changes equivalent to one fifth of those seen with oral bisphosphonate treatment (SD 1) [15]. Assuming a 20% dropout rate, an alpha error of 5% and a power of 80%, 60…”

Section: Discussionmentioning

confidence: 99%

“…This study was thus powered to detect a change in LS-aBMD z-score of 0.2 which is the equivalent to one fifth of the changes occasioned by bisphosphonate treatments [15].…”

Section: Sample Sizementioning

confidence: 99%

“…Bisphosphonates are widely used to increase BMD in children with OI [10][11][12][13], leading to increments in lumbar spine areal BMD (LS-aBMD) [10,14,15]. Adequate intake of calcium and vitamin D is likely to optimize response to bisphosphonate treatments by preventing symptomatic hypocalcemia [13,16] .…”

Section: Introductionmentioning

confidence: 99%

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Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial

Plante

Veilleux

Glorieux

et al. 2016

Bone

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Background Osteogenesis imperfecta (OI) is a genetic disease characterized by fragile bones and short stature. Recently, a positive association was found between serum 25‐hydroxyvitamin D (25OHD) concentrations and lumbar spine areal bone mineral density (LS‐aBMD) z‐scores in this population. Objectives: To assess whether high‐dose vitamin D supplementation (2000 IU) will result in significantly higher LS‐aBMD z‐scores after one‐year; and to evaluate the effect of vitamin D supplementation on lower limb muscle power. Results: At baseline, average serum 25OHD concentration was 65.6 nmol/L (SD 20.4) with no difference seen between treatment groups (p=0.77). Deficient serum 25OHD concentrations (<50 nmol/L) were measured in only 21% of patients at baseline. Supplementation resulted in higher serum 25OHD concentrations in almost all participants (90%) with significantly higher increases seen with 2000 IU (mean [95% C.I.] = 30.5 nmol/L [21.3; 39.6] vs 15.2 nmol/L [6.4; 24.1], p= 0.02). No significant changes were detected in BMD measurements or in lower limb muscle power between treatment groups from baseline to final visit. Conclusions Supplementation with either 400 or 2000 IU of vitamin D translates into significant increases in serum 25OHD concentrations in children with OI. However, increases in baseline serum 25OHD concentrations already within a healthy range (蠅50 nmol/L) do not translate into increases in BMD z‐scores in children with OI. This research was supported by the Shriners Hospital for Children as well as by The Network for Oral and Bone Health Research.

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Section: Discussionmentioning

confidence: 99%

“…This study was thus powered to detect a change in LS-aBMD z-score of 0.2 which is the equivalent to one fifth of the changes occasioned by bisphosphonate treatments [15].…”

Section: Sample Sizementioning

confidence: 99%

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Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial

Plante

Veilleux

Glorieux

et al. 2016

Bone

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“…Existing treatments largely provide symptomatic relief, but there is currently no cure. The gold standard bisphosphonates temporarily improve bone strength by inhibiting bone resorption, but they do not improve growth or bone pain beyond a year [5] and do not reduce fracture incidence long term [6].…”

Section: Introductionmentioning

confidence: 99%

Potential of Human Fetal Chorionic Stem Cells for the Treatment of Osteogenesis Imperfecta

Jones

Moschidou

Abdulrazzak

et al. 2014

Stem Cells and Development

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Osteogenesis imperfecta (OI) is a genetic bone pathology with prenatal onset, characterized by brittle bones in response to abnormal collagen composition. There is presently no cure for OI. We previously showed that human first trimester fetal blood mesenchymal stem cells (MSCs) transplanted into a murine OI model (oim mice) improved the phenotype. However, the clinical use of fetal MSC is constrained by their limited number and low availability. In contrast, human fetal early chorionic stem cells (e-CSC) can be used without ethical restrictions and isolated in high numbers from the placenta during ongoing pregnancy. Here, we show that intraperitoneal injection of e-CSC in oim neonates reduced fractures, increased bone ductility and bone volume (BV), increased the numbers of hypertrophic chondrocytes, and upregulated endogenous genes involved in endochondral and intramembranous ossification. Exogenous cells preferentially homed to long bone epiphyses, expressed osteoblast genes, and produced collagen COL1A2. Together, our data suggest that exogenous cells decrease bone brittleness and BV by directly differentiating to osteoblasts and indirectly stimulating host chondrogenesis and osteogenesis. In conclusion, the placenta is a practical source of stem cells for the treatment of OI.

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“…17 Akçay ve ark.nın 2008 yılında 12 hastalık alendronat deneyimlerinin yayınlandığı çalışmada, alendronatın kırık oranını anlamlı şekilde azalttığı görülmüştür. L2-L4 T skoru -4,6 dan -2,7'ye gerilemiştir.…”

Section: Olgu Sunumlariunclassified

Features of 9 Adult Cases of Osteogenesis Imperfecta

Kutbay¹,

Yürekli²,

Keklik³

et al. 2015

Turkiye Klinikleri J Endocrin

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24O steogenezis imperfekta (Oİ) yaygın osteoporoz, tekrarlayan kemik kırıkları ve bunun sonucunda oluşan deformitelerle karakterize genetik bir hastalıktır. Oİ'nin insidansı farklı tipleri birlikte düşü-nüldüğünde 15 000-20 000 doğumda 1'dir. 1 Temel patoloji, Tip 1 kollajen zincirlerini kodlayan COL1A1 ya da COL1A2 genindeki mutasyonlardır. COL1A1 ve COL1A2 genindeki mutasyonlar Tip 1 kollajenin yapısını ya da miktarını değiştirerek, Oİ'nin subklinik fenotipinden ölümcül fenotipine kadar geniş aralıktaki iskelete ait klinik tablosunu oluşturur. 1 Hastalık tipik Osteogenezis İmperfektalı 9 Erişkin Olgunun Özellikleri Ö ÖZ ZE ET T Osteogenezis imperfekta yaygın osteoporoz, tekrarlayan kemik kırıkları ve bunun sonucunda oluşan deformitelerle karakterize genetik bir hastalıktır. Çoğu vakada Tip1 kollajen yapımından sorumlu COL1A1 veya COL1A2 genlerinden birinde dominant bir mutasyon sonucu gelişir. Osteogenezis imperfektalı olguların tedavisinde hedef; kırıkları ve ağrıyı azaltmak, uzun dönem kemik deformitelerini önleyerek kişinin fonksiyonel kapasitesini artırmak ve mobilizasyonunu sağla-maktır. Bu çalışmada, osteogenezis imperfektalı 9 olgu retrospektif olarak incelendi. Olguların yaşı, cinsiyeti, aile anamnezi, başvuru yaşları, hastalığın başlama yaşı, kırık sayıları, kemik mineral dansitesi T ve Z skorları, aldıkları tedavi ve süreleri, kemik yapım-yıkım belirteçleri, 25-OH D vitamin düzeyleri değerlendirildi. Bu çalışmada, ikisi erkek yedisi kadın toplam 9 olgu retrospektif olarak incelendi. Olguların ortalama yaşı 24 idi. Tanı yaşları 1,5-15 arasında değişmekte idi. Oral alendronat, pamidronat ve zoledronik asit alan olgularımızda son dönemde yeni kırık oluşumu gözlen-medi.A An na ah h t ta ar r K Ke e l li i m me e l le er r: : Osteogenezis imperfekta; kırıklar, kemik; pamidronat A AB BS S T TR RA AC CT T Osteogenesis imperfecta is a congenital bone disorder characterized by osteoporosis, recurrent fractures and deformities. Most cases are caused by mutations in the COL1A1 and COL1A2 genes responsible for Type-1 collagen production. Treatment of the patients with OI is aimed at increasing bone strength and personal functionality in order to prevent fracture and maintain mobility and decrease pain. Nine cases of OI (n=7 F, n=2 M) were retrospectively investigated. In this study, following parameters were evaluated: the age, gender, family medical history, duration of disease, frequency of fractures, bone mineral density scores, duration and types of medical therapy, bone turnover markers, the level of 25(OH) vitamin D. The mean of age of our patients was 24. The age at the time of diagnosis was between 1,5 and 15 years old. Oral alendronate, pamidronat and zoledronic acid were given and no fracture was observed with this bisphosphonates treatment.K Ke ey y W Wo or rd ds s: : Osteogenesis imperfecta; fractures, bone; pamidronate T Tu ur rk ki iy ye e K Kl li in ni ik kl le er ri i J J E En nd do oc cr ri in n 2 20 01 15 5; ;1 10 0( (1 1) ): :2 24 4--3 30 0

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Alendronate for the Treatment of Pediatric Osteogenesis Imperfecta: A Randomized Placebo-Controlled Study

Abstract: Oral ALN for 2 yr in pediatric patients with OI significantly decreased bone turnover and increased spine areal BMD but was not associated with improved fracture outcomes.

Cited by 191 publications

References 37 publications

Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial

Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial

Potential of Human Fetal Chorionic Stem Cells for the Treatment of Osteogenesis Imperfecta

Features of 9 Adult Cases of Osteogenesis Imperfecta

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