Recent developments in osteogenesis imperfecta

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Shaker" }, { "@type": "Person", "name": "Carolyne Albert" }, { "@type": "Person", "name": "Jessica Fritz" }, { "@type": "Person", "name": "Gerald Harris" } ], "publisher": { "@type": "Organization", "name": "F1000Research", "logo": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 480, "width": 60 } }, "image": { "@type": "ImageObject", "url": "https://f1000research.com/img/AMP/F1000Research_image.png", "height": 1200, "width": 150 }, "description": "Osteogenesis imperfecta (OI) is an uncommon genetic bone disease associated with brittle bones and fractures in children and adults. Although OI is most commonly associated with mutations of the genes for type I collagen, many other genes (some associated with type I collagen processing) have now been identified. The genetics of OI and advances in our understanding of the biomechanical properties of OI bone are reviewed in this article. Treatment includes physiotherapy, fall prevention, and sometimes orthopedic procedures. In this brief review, we will also discuss current understanding of pharmacologic therapies for treatment of OI." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/4-681/v1/iparadigms", "name": "Recent developments in osteogenesis imperfecta" } } ] } Home Browse Recent developments in osteogenesis imperfecta ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Shaker JL, Albert C, Fritz J and Harris G. Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.12688/f1000research.6398.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Review Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] Joseph L. Shaker 1 , Carolyne Albert 2,3 , Jessica Fritz 2 , Gerald Harris 2,3 Joseph L. Shaker 1 , Carolyne Albert 2,3 , Jessica Fritz 2 , Gerald Harris 2,3 PUBLISHED 07 Sep 2015 Author details Author details 1 Endocrinology, Medical College of Wisconsin, Milwaukee, WI, USA 2 Orthopaedic and Rehabilitation Engineering Center, Marquette University and Medical College of Wisconsin, Milwaukee, WI, USA 3 Shriners Hospitals for Children, Chicago, IL, USA OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Osteogenesis imperfecta (OI) is an uncommon genetic bone disease associated with brittle bones and fractures in children and adults. Although OI is most commonly associated with mutations of the genes for type I collagen, many other genes (some associated with type I collagen processing) have now been identified. The genetics of OI and advances in our understanding of the biomechanical properties of OI bone are reviewed in this article. Treatment includes physiotherapy, fall prevention, and sometimes orthopedic procedures. In this brief review, we will also discuss current understanding of pharmacologic therapies for treatment of OI. READ ALL READ LESS Keywords Osteogenesis imperfecta, mutations, recessive Corresponding Author(s) Joseph L. Shaker ( [email protected] ) Close Corresponding author: Joseph L. Shaker Competing interests: JS is a consultant for Alexion Pharmaceuticals. The other authors declare that they have no competing interests. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2015 Shaker JL et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Shaker JL, Albert C, Fritz J and Harris G. Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.12688/f1000research.6398.1 ) First published: 07 Sep 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.12688/f1000research.6398.1 ) Latest published: 07 Sep 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.12688/f1000research.6398.1 ) Introduction Osteogenesis imperfecta (OI) is an unusual heritable disease that occurs in about 1 in 10,000 to 20,000 live births 1 . The major clinical manifestation is skeletal fragility. Skeletal deformity, joint laxity, and scoliosis may be present 2 . Other extraskeletal manifestations include hearing loss, dentinogenesis imperfecta, blue/gray sclerae, hypercalciuria, aortic root dilatation, and neurologic conditions such as macrocephaly, hydrocephalus, and basilar invagination 1 – 5 . The phenotype is variable, ranging from osteoporosis presenting in adulthood to lethality in children 3 . Even adults with “mild” OI may have significant musculoskeletal symptoms, including arthritis, fractures, back pain, scoliosis, and tendon ruptures 6 . About 90% of patients have mutations in type I collagen genes ( COL1A1 and COL1A2 ) 3 ; however, many other genes have now been described. Some of the genes encode proteins related to type I collagen (for example, enzymes that modify type I collagen, chaperone proteins, and signaling proteins). In 1979, Sillence et al . proposed a classification system for OI with four types based on severity: type I mild non-deforming, type II perinatal lethal, type III severely deforming, and type IV moderately deforming 7 . This classification has been expanded as new genes were discovered. Phenotypic classification (types I to V with multiple genes included in some of the types) has been proposed 5 . Alternatively, classification by genetics has been proposed (see Table 1 ), which was created through modifications of references 8 – 10 . Table 1. Classification of osteogenesis imperfecta. Type Inheritance Gene Protein Defect Phenotype I AD COLA1/COLA2 α1(1) collagen Collagen quantity Mild, non-deforming II AD COLA1/COLA2 α1(1)/α2(1) collagen Collagen structure Perinatal lethal III AD COLA1/COLA2 α1(1)/α2(1) collagen Collagen structure Progressively deforming IV AD COLA1/COLA2 α1(1)/α2(1) collagen Collagen structure Moderately deforming V AD IFITM5 BRIL Matrix mineralization Moderate, distinct histology VI AR SERPINF1 PEDF Moderate to severe, distinct histology VII AR CRTAP CRTAP Prolyl 3 hydroxylation Severe to lethal VIII AR LEPRE1 P3H1 Prolyl 3 hydroxylation Severe to lethal IX AR PPIB CyPB Prolyl 3 hydroxylation Moderate to lethal X AR SERPINH1 HSP47 Collagen chaperoning Severe XI AR FKBP10 FKBP65 Telopeptide hydroxylation Progressively deforming (Bruck syndrome) XII AR SP7 SP7/osterix Osteoblast development Moderate XIII AR BMP1 BMP1/mTLD Collagen processing Severe, high bone mass XIV AR TMEM38B TRIC-B Cation channel defect Moderate to severe XV AR WNT1 WNT1 Variable XV AD WNT1 WNT1 Early-onset osteoporosis Others AR CREB3L1 Oasis COL1A1 transcription Progressively deforming XL PLS3 Plastin Osteocyte defect Mild AR PLOD2 Lysyl hydroxylase 2 Collagen telopeptide hydroxylation Progressively deforming AD, autosomal dominant; AR, autosomal recessive; XL, x-linked. There have been recent advances in the understanding of the structure and mechanical properties of bone in children with OI. These advances may lead to improved finite element (FE) models that help predict fracture risk of specific activities and help plan physiotherapy. In addition to physiotherapy and orthopedic surgery when needed, intravenous bisphosphonates have been used extensively in moderate to severe OI in childhood. Less is known about pharmacologic treatment in adults. Anabolic therapy with PTH 1-34 has been studied in adults with OI. Future therapies may include antibodies to sclerostin, transforming growth factor beta (TGFβ) antagonism, gene therapy, and cell-based therapies. Genes and classification OI is most commonly caused by mutations in type I collagen. Type I collagen is a rod-like structure formed from a trimer of 2 COL1A1 and 1 COL1A2 subunits 3 , which requires post-translational modification. Many of the other rare forms of OI are due to defects in proteins involved in cross-linking, hydroxylation, and mineralization of type I collagen. Mutations of CRTAP , which encodes cartilage-associated protein, have been shown to cause recessive OI 11 – 14 . Mutations of LEPRE1 , which encodes prolyl 3 hydroxylase 14 – 16 , and PPIB (protein cyclophylin B) 17 – 19 also cause recessive OI. The proteins described above form a complex that modifies specific prolines in the collagen and these mutations result in moderate to lethal OI. SERPINH1 mutations cause severe recessive OI 20 . The protein affected in SERPINH1 mutations, HSP47, is a collagen chaperone protein 8 . FKBP10 mutations cause recessive OI (progressively deforming) 21 . This gene encodes the protein FKBP65, which appears to be needed for hydroxylation of collagen telopetide lysine 22 . Both HSP47 and FKBP65 are needed for the proper folding of the collagen triple helix. Furthermore, Bruck syndrome (OI and congenital contractures) can be caused by homozygous mutations on FKPB10 23 , and Kuskokwim syndrome (congenital contractures with mild skeletal problems seen in Yup’ik people in Alaska) is caused by FKBP10 mutations 24 . PLOD2 mutations also cause recessive OI 25 . PLOD-2 encodes lysyl hydroxylase 2, which hydroxylates collagen telopeptide lysine. Bruck syndrome can also be caused by homozygous mutations of PLOD2 25 . BMP1 (bone morphogenetic protein 1) mutations also cause recessive OI 26 , 27 . The protein, BMP1, is a protease that cleaves the c-propeptide of type I collagen 26 , 27 but also has other substrates. SP7 mutations cause recessive OI 28 . SP7 encodes the protein osterix, which may be needed for osteoblast differentiation 10 . WNT1 mutations 29 – 31 have been reported in early-onset osteoporosis (dominant) and OI (recessive). The protein, WNT1, may be important in the beta catenin system, which stimulates bone formation 29 – 31 . TMEM38B mutations have been reported in recessive OI 32 . This gene encodes TRIC-B, which may be important in intracellular calcium signaling. Defective TRIC-B may cause bone disease through defective calcium signaling in bone cells 10 . CREB3L1 mutations cause recessive OI 33 . CREB3L1 encodes the protein OASIS, which may activate transcription of COL1A1 34 . PLS3 (plastin 3) mutations have been reported in x-linked osteoporosis 35 – 37 . Plastin 3 is expressed in osteocyte dendrites and may be important in mechanosensing 35 . Bone biopsies from patients with PLS3 mutations have shown cortical and trabecular osteoporosis with normal to low bone formation rates 36 , 37 . There is no mineralization defect 36 , 37 . Mutations in IFITM5 , a bone-restricted IFITM-like protein (BRIL) (dominant) cause type V OI 38 – 42 . These patients have prominent callus formation and ossification of the forearm interosseous membrane 38 – 42 . They also have mesh-like lamellation on bone biopsy as well as a mineralization defect 38 – 42 . There appear to be substantial differences in phenotypic presentation even with similar mutations 40 – 42 . Type VI OI is caused by mutations in SERPINF1 (protein PEDF) 43 , 44 . Children with type VI OI have elevated alkaline phosphatase, and bone biopsy reveals fish-scale pattern under polarized light as well as broad bands of unmineralized osteoid 43 , 44 . Interestingly, some patients with BRIL mutations have phenotypic type VI OI (rather than type V) 45 . BRIL and PEDF are related, and it appears that mutations causing gain-of-function of BRIL cause OI type V and that those causing loss-of-function of BRIL look phenotypically like OI type VI 46 . Structure and mechanical properties of bones in osteogenesis imperfecta From a mechanical perspective, increased fracture risk in individuals with OI could stem from a combination of reduced bone mass, decreased bone material quality, and, in some individuals, the presence of bone deformity. Bone mass Low bone mass is a clinical characteristic of OI, and individuals with this disorder tend to have markedly reduced areal bone mineral density (BMD) 47 – 49 . This reduced bone mass can be the consequence of decreased bone size or decreased volumetric BMD or both 49 , 50 . Studies of iliac crest biopsies have revealed lower bone tissue quantity in children with moderate and severe OI, including reduced bone volume fraction, and decreased trabecular and cortical thicknesses 51 – 53 . Decreased bone volume, though less marked, was also noted in some children with mild OI 51 , 52 . In cortical bone specimens from the long bone shafts of children with OI, “atypical, flattened, and large resorption lacunae” 54 and abnormally elevated porosity have been observed 54 – 57 . For example, an average intracortical vascular porosity of 21% was found in bone shaft osteotomies from children with OI by synchrotron radiation micro-computed tomography 55 , 57 ; the corresponding value in normal pediatric bones was 3% 57 . From a structural perspective, reduced bone mass can lead to increased stresses within the bone as a result of a smaller area of bone tissue present to support physiological loads. For this reason, low bone mass is likely a considerable contributor to bone fragility in OI. Bone material quality In addition to the structural deficiency (low bone mass), mechanical quality of the bone material in OI is reduced. The genetic defects causing OI affect type I collagen, the main organic component of bone. As discussed earlier, most forms of OI (types I to IV) are attributed to insufficient collagen production or amino acid substitution defects within the collagen molecules or both 58 – 63 , and less common recessive forms have been associated with abnormalities in other proteins that interact with type I collagen 9 , 64 . Since type I collagen is an integral component of bone tissues, it should be no surprise that abnormalities affecting this protein would impact bone material quality. At the ultrastructural level, irregularities in collagen and mineral geometry as well as abnormalities in mineral composition have been reported 65 – 70 . Studies in mice indicated that the material abnormalities in OI have a negative impact on bone material properties 71 – 76 . A few studies have also used biopsy and osteotomy specimens to measure bone material properties in humans with this disorder. Some of these studies used nanoindentation, a technique in which a diamond-tip indenter is pressed into the polished surface of a material (in this case, bone), creating an indent a few microns in size. With this test, elastic modulus and hardness—that is, properties representing the material’s resistance to elastic (recoverable) and plastic (non-recoverable) deformation, respectively—are determined at the submicrostructural level. Based on nanoindentation, slightly higher elastic modulus and hardness were found in children with mild (type I) versus severe (type III) OI 77 , whereas these properties were not found to differ between children with severe (type III) versus moderately severe (type IV) phenotypes 78 . However, exactly how these properties compare with normal tissues remains unclear; one study reported higher elastic modulus and hardness in children with severe OI versus controls 79 , whereas another reported the opposite 80 . Furthermore, bone tissues have a complex hierarchical structure, which results in properties that differ between length scales, and nanoindentation provides only limited insight regarding bone tissue properties at the submicrostructural scale. Another limitation with this technique is that it does not measure strength, a property representing the ability of a material to carry stress without breaking or sustaining damage. Recent studies have measured cortical bone material properties, including strength, at a larger scale by using surgical bone specimens from long bone diaphyses of children with OI 55 , 56 , 81 . In these studies, small osteotomy specimens were machined into parallelepiped-shaped specimens and loaded to failure in either bending 55 , 81 or compression 56 . Bone material strength was confirmed to be lower than normal in these children, and this property was found to be negatively related to an abnormally elevated intracortical porosity. These findings suggest that increased cortical porosity contributes to increased risk of long bone fractures in OI. Bone deformity In addition to decreased bone mass and reduced bone material quality (low bone material strength), deformities of the spine and long bones are common in OI. For example, children with severe OI often exhibit anterolateral bowing of the femur and anterior bowing of the tibia 7 , 47 . Increased curvature in long bones leads to an increase in maximum stresses within the bone shaft 82 . The increased stresses attributed to bone deformities in OI can further contribute to the risk of bone fracture. Fracture prediction based on mechanical models Mechanical modeling through the use of FE analysis is a well-established technique that allows detailed analysis of composite structures under a variety of load conditions. In the field of orthopedic biomechanics, FE modeling is frequently used to examine the responses of bone to loading 83 – 86 . Patient-specific FE models have been effective for bone strain and fracture strength assessment, and as recently as 2009 Fritz et al . applied these models to predict fractures in OI 87 , 88 . A femoral model including muscle forces was analyzed during all seven phases of the gait cycle and geometrically matched to bone anatomy with x-rays. The most current work includes advanced meshing techniques for improved geometric biofidelity and updated mechanical property data 55 . Other FE models for assessing OI bones have also been reported. Orwoll et al . used FE modeling to estimate vertebral strength in a study of the effects of teriparatide treatment in adults with OI 89 . Caouette et al . developed an FE model to assess fracture risk at the tibia in children with OI 90 . This tibia model examined fracture risk during two-legged hopping, lateral loading, and torsional loading. Future applications of FE modeling may prove invaluable for better quantification of fracture risk in OI. These models could help identify activities that pose greater risk of fracture and, through appropriate controls, may enable persons with OI to participate safely and more fully in a greater spectrum of daily and recreational activities. Management Physical therapy The goals of the treatment in OI are to decrease pain and fractures and to maximize mobility. Physical therapy/rehabilitation 91 is particularly important in children to improve weight bearing and prevent fractures as well as to increase strength and mobility during fracture recovery. Some children may require wheelchairs or walking aids. Occupational therapy may be needed to help with daily living activities. Pharmacologic therapy Bisphosphonates Bisphosphonates (BPs) are non-hydrolysable synthetic analogs of pyrophosphate 92 . BPs adhere to mineralized surfaces, inhibit osteoclastic bone resorption, and have very long skeletal half-lives 92 . Intravenous BPs are currently the primary treatment of children with moderate to severe OI. BPs increase BMD and size in children with OI 49 . BPs do not appear to impair bone formation that increases cortical width in children with OI 93 . Observational studies suggest decreased fractures 94 , 95 , decreased bone pain, and improved vertebral shape 94 , 95 . Ability to perform activities of daily living may also be improved. However, it has been difficult to confirm all of these benefits in randomized trials, and the optimal duration of BP treatment is unknown. In a study of children with predominantly mild OI, oral risedronate increased BMD and appeared to decrease clinical fractures 96 . Atypical fractures have been reported in children with OI treated with bisphosphonates 97 , 98 ; however, osteneocrosis of the jaw does not appear to be a major problem in children with OI treated with BPs 99 – 101 . Several studies have been done on the use of intravenous or oral BPs in adults with OI. Although BMD increases have been reported during these treatments, fracture data are equivocal 102 – 106 . A Cochrane review found increased BMD in patients with OI treated with BPs but did not find definitive evidence of fracture reduction 107 . Furthermore, a recent meta-analysis of placebo-controlled trials suggested that the effects of BPs for fracture prevention in OI were inconclusive 108 . Growth hormone Growth hormone has anabolic effects on bone. A 1-year randomized trial of the BP, neridronate, with or without growth hormone showed greater increase in BMD and growth velocity with growth hormone, but there was no fracture benefit of growth hormone 109 . Teriparatide Teriparatide (PTH1-34) is an anabolic agent that stimulates bone formation (and ultimately bone resorption). This drug decreases vertebral and non-vertebral fractures in post-menopausal women with osteoporosis 110 . Observational data in adults with OI suggest increased BMD with teriparatide 107 , 111 . Recently, a randomized trial of teriparatide in adults with OI showed increased BMD as well as increased vertebral strength estimated by FE analysis 91 . The benefits appeared to occur in mild (type I) OI but not in more severe OI (types III and IV). Denosumab Denosumab is a monoclonal antibody to receptor activator of nuclear factor kappa B ligand that decreases bone resorption, increases bone density, and reduces fractures in women with post-menopausal osteoporosis 112 . This drug may represent a future therapy in OI. In a study of four children with type VI OI, increased BMD and mobility and improved vertebral shape were reported after denosumab treatment, and the outcomes of this study indicated that this treatment appears to be safe 113 . There is also a report of denosumab use in two children with OI caused by COL1A1/A2 mutations 114 . As with BPs, “zebra lines” were present, suggesting continued longitudinal growth 114 . Denosumab has been reported to cause hypophosphatemia, hypocalcemia, and secondary hyperparathyroidism in a child with fibrous dysplasia of bone 115 . There was rebound hypercalcemia after stopping denosumab 115 . Possible future therapies Sclerostin is an inhibitor of the LRP5/WnT system that decreases bone formation. Antibodies to sclerostin are in clinical trials for treatment of osteoporosis with the goal to increase bone density 116 . Sclerostin antibody appeared to be effective in a mouse model of moderately severe OI 117 , 118 but less so in a mouse model of more severe OI 119 . TGFβ is secreted by osteoblasts and increases osteoclastic bone resorption 120 . Excessive TGFβ signaling may be important in some forms of OI, and anti-TGFβ therapy represents an interesting prospect for the future treatment of OI 120 . Cell-based therapy, such as bone marrow 121 or mesenchymal stem cell 122 – 124 transplantation, has also been investigated and may have promise; but these could also have significant risks. Gene therapy with allele-specific silencing may represent a future therapy 125 . Summary Although most cases of OI are caused by COL1A1/A2 mutations, many new genetic causes have been identified in recent years. Some of these genes are related to the processing of type I collagen. Furthermore, we have greater understanding of the biomechanics of OI bone, including material properties, muscle and gait load effects, and fracture strength assessment. Biomechanical models could help identify activities that pose greater risk of fracture and, through appropriate controls, may enable persons with OI to participate safely and more fully in a greater spectrum of activities. Physical therapy is an important part of the management of these patients. Intravenous BPs are commonly used in children with moderate to severe OI. Some of the benefits seen in observational studies have been hard to prove in controlled studies. Treatment of adults with OI is less well studied. BPs and teriparatide appear to increase BMD, but fracture data are lacking. Teriparatide appears to increase bone strength as estimated by FE analysis in adults with mild OI. Other promising treatments for OI are under investigation. Competing interests JS is a consultant for Alexion Pharmaceuticals. The other authors declare that they have no competing interests. Grant information The author(s) declared that no grants were involved in supporting this work. F1000 recommended References 1. Monti E, Mottes M, Fraschini P, et al. : Current and emerging treatments for the management of osteogenesis imperfecta. Ther Clin Risk Manag. 2010; 6 : 367–81. PubMed Abstract | Publisher Full Text | Free Full Text 2. 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PubMed Abstract | F1000 Recommendation 91. Hoyer-Kuhn H, Semler O, Stark C, et al. : A specialized rehabilitation approach improves mobility in children with osteogenesis imperfecta. J Musculoskelet Neuronal Interact. 2014; 14 (4): 445–53. PubMed Abstract | F1000 Recommendation 92. Licata AA: Discovery, clinical development, and therapeutic uses of bisphosphonates. Ann Pharmacother. 2005; 39 (4): 668–77. PubMed Abstract | Publisher Full Text 93. Rauch F, Travers R, Plotkin H, et al. : The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. J Clin Invest. 2002; 110 (9): 1293–9. PubMed Abstract | Publisher Full Text | Free Full Text 94. Plotkin H, Rauch F, Bishop NJ, et al. : Pamidronate treatment of severe osteogenesis imperfecta in children under 3 years of age. J Clin Endocrinol Metab. 2000; 85 (5): 1846–50. PubMed Abstract | Publisher Full Text 95. Land C, Rauch F, Munns CF, et al. : Vertebral morphometry in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate treatment. Bone. 2006; 39 (4): 901–6. PubMed Abstract | Publisher Full Text 96. Bishop N, Adami S, Ahmed SF, et al. : Risedronate in children with osteogenesis imperfecta: a randomised, double-blind, placebo-controlled trial. Lancet. 2013; 382 (9902): 1424–32. PubMed Abstract | Publisher Full Text | F1000 Recommendation 97. Nicolaou N, Agrawal Y, Padman M, et al. : Changing pattern of femoral fractures in osteogenesis imperfecta with prolonged use of bisphosphonates. J Child Orthop. 2012; 6 (1): 21–7. PubMed Abstract | Publisher Full Text | Free Full Text 98. Carpintero P, Del Fresno JA, Ruiz-Sanz J, et al. : Atypical fracture in a child with osteogenesis imperfecta. Joint Bone Spine. 2015; 82 (4): 287–8. PubMed Abstract | Publisher Full Text 99. Malmgren B, Aström E, Söderhäll S: No osteonecrosis in jaws of young patients with osteogenesis imperfecta treated with bisphosphonates. J Oral Pathol Med. 2008; 37 (4): 196–200. PubMed Abstract | Publisher Full Text 100. Chahine C, Cheung MS, Head TW, et al. : Tooth extraction socket healing in pediatric patients treated with intravenous pamidronate. J Pediatr. 2008; 153 (5): 719–20. PubMed Abstract | Publisher Full Text 101. Hennedige AA, Jayasinghe J, Khajeh J, et al. : Systematic review on the incidence of bisphosphonate related osteonecrosis of the jaw in children diagnosed with osteogenesis imperfecta. J Oral Maxillofac Res. 2014; 4 (4): e1. PubMed Abstract | Free Full Text 102. Adami S, Gatti D, Colapietro F, et al. : Intravenous neridronate in adults with osteogenesis imperfecta. J Bone Miner Res. 2003; 18 (1): 126–30. PubMed Abstract | Publisher Full Text 103. Chevrel G, Schott AM, Fontanges E, et al. : Effects of oral alendronate on BMD in adult patients with osteogenesis imperfecta: a 3-year randomized placebo-controlled trial. J Bone Miner Res. 2006; 21 (2): 300–6. PubMed Abstract | Publisher Full Text 104. Shapiro JR, Thompson CB, Wu Y, et al. : Bone mineral density and fracture rate in response to intravenous and oral bisphosphonates in adult osteogenesis imperfecta. Calcif Tissue Int. 2010; 87 (2): 120–9. PubMed Abstract | Publisher Full Text 105. Bradbury LA, Barlow S, Geoghegan F, et al. : Risedronate in adults with osteogenesis imperfecta type I: increased bone mineral density and decreased bone turnover, but high fracture rate persists. Osteoporos Int. 2012; 23 (1): 285–94. PubMed Abstract | Publisher Full Text 106. O'Sullivan ES, van der Kamp S, Kilbane M, et al. : Osteogenesis imperfecta in adults: phenotypic characteristics and response to treatment in an Irish cohort. Ir J Med Sci. 2014; 183 (2): 225–30. PubMed Abstract | Publisher Full Text 107. Phillipi CA, Remmington T, Steiner RD: Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2008; (4): CD005088. PubMed Abstract | Publisher Full Text | F1000 Recommendation 108. Hald JD, Evangelou E, Langdahl BL, et al. : Bisphosphonates for the prevention of fractures in osteogenesis imperfecta: meta-analysis of placebo-controlled trials. J Bone Miner Res. 2015; 30 (5): 929–33. PubMed Abstract | Publisher Full Text | F1000 Recommendation 109. Antoniazzi F, Monti E, Venturi G, et al. : GH in combination with bisphosphonate treatment in osteogenesis imperfecta. Eur J Endocrinol. 2010; 163 (3): 479–87. PubMed Abstract | Publisher Full Text | F1000 Recommendation 110. Neer RM, Arnaud CD, Zanchetta JR, et al. : Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001; 344 (19): 1434–41. PubMed Abstract | Publisher Full Text 111. Gatti D, Rossini M, Viapiana O, et al. : Teriparatide treatment in adult patients with osteogenesis imperfecta type I. Calcif Tissue Int. 2013; 93 (5): 448–52. PubMed Abstract | Publisher Full Text | F1000 Recommendation 112. Cummings SR, San Martin J, McClung MR, et al. : Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009; 361 (8): 756–65. PubMed Abstract | Publisher Full Text | F1000 Recommendation 113. Hoyer-Kuhn H, Netzer C, Koerber F, et al. : Two years' experience with denosumab for children with osteogenesis imperfecta type VI. Orphanet J Rare Dis. 2014; 9 : 145. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 114. Hoyer-Kuhn H, Semler O, Schoenau E: Effect of denosumab on the growing skeleton in osteogenesis imperfecta. J Clin Endocrinol Metab. 2014; 99 (11): 3954–5. PubMed Abstract | Publisher Full Text 115. Boyce AM, Chong WH, Yao J, et al. : Denosumab treatment for fibrous dysplasia. J Bone Miner Res. 2012; 27 (7): 1462–70. PubMed Abstract | Publisher Full Text | Free Full Text 116. McClung MR, Grauer A, Boonen S, et al. : Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med. 2014; 370 (5): 412–20. PubMed Abstract | Publisher Full Text | F1000 Recommendation 117. Sinder BP, Eddy MM, Ominsky MS, et al. : Sclerostin antibody improves skeletal parameters in a Brtl/+ mouse model of osteogenesis imperfecta. J Bone Miner Res. 2013; 28 (1): 73–80. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 118. Sinder BP, White LE, Salemi JD, et al. : Adult Brtl/+ mouse model of osteogenesis imperfecta demonstrates anabolic response to sclerostin antibody treatment with increased bone mass and strength. Osteoporos Int. 2014; 25 (8): 2097–107. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 119. Roschger A, Roschger P, Keplingter P, et al. : Effect of sclerostin antibody treatment in a mouse model of severe osteogenesis imperfecta. Bone. 2014; 66 : 182–8. PubMed Abstract | Publisher Full Text | F1000 Recommendation 120. Grafe I, Yang T, Alexander S, et al. : Excessive transforming growth factor-β signaling is a common mechanism in osteogenesis imperfecta. Nat Med. 2014; 20 (6): 670–5. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 121. Horwitz EM, Prockop DJ, Gordon PL, et al. : Clinical responses to bone marrow transplantation in children with severe osteogenesis imperfecta. Blood. 2001; 97 (5): 1227–31. PubMed Abstract | Publisher Full Text 122. Horwitz EM, Gordon PL, Koo WK, et al. : Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci U S A. 2002; 99 (13): 8932–7. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation 123. Le Blanc K, Götherström C, Ringdén O, et al. : Fetal mesenchymal stem-cell engraftment in bone after in utero transplantation in a patient with severe osteogenesis imperfecta. Transplantation. 2005; 79 (11): 1607–14. PubMed Abstract | Publisher Full Text | F1000 Recommendation 124. Amin MT, Shazly SA: In utero stem cell transplantation for radical treatment of osteogenesis imperfecta: perspectives and controversies. Am J Perinatol. 2014; 31 (10): 829–36. PubMed Abstract | Publisher Full Text 125. Lindahl K, Kindmark A, Laxman N, et al. : Allele dependent silencing of collagen type I using small interfering RNAs targeting 3'UTR Indels - a novel therapeutic approach in osteogenesis imperfecta. Int J Med Sci. 2013; 10 (10): 1333–43. PubMed Abstract | Publisher Full Text | Free Full Text | F1000 Recommendation Comments on this article Comments (1) Version 1 VERSION 1 PUBLISHED 07 Sep 2015 Reader Comment 01 Oct 2015 Raymond Dalgleish , University of Leicester, UK 01 Oct 2015 Reader Comment I have noted a few issues in this article: On page 2, in the section headed "Genes and classification", gene symbols ( COLIA1 and COL1A2 ) are inappropriately used to designate the component ... Continue reading I have noted a few issues in this article: On page 2, in the section headed "Genes and classification", gene symbols ( COLIA1 and COL1A2 ) are inappropriately used to designate the component protein chains of type I collagen. Gene symbols and protein product names should not be used interchangeably. The protein chains are α1(I) and α2(I) respectively. In Table 1, the gene symbols for the mutant genes leading to OI types I, II, III and IV are incorrect. They should be COL1A1 and COL1A2 , not COL1A1 and COLA2 . In Table 1, the gene symbol for the gene encoding the protein prolyl-3 hydroxylase is P3H1 , not LEPRE1 . The gene symbol for this gene was changed to P3H1 in December 2014. Table 1 continues to propagate the notion that there are very many OI types when, in reality, there are really only five true types which can be clearly distinguished clinically (types I to V). The problem has been caused by several new OI types being created to correspond to newly discovered genes which harbour OI-causing sequence variants. This has only served to confuse matters and is discussed at length by Van Dijk and Sillence (2014) ( http://www.ncbi.nlm.nih.gov/pubmed/24715559 ). It is perhaps unsurprising that the article gives emphasis to pharmacological interventions for OI, given that one of the authors is employed by Alexion Pharmaceuticals, but it is improper to ignore surgical interventions such as rodding of long bones and mesenchymal stem cell therapy. There is no mention in the article of the fact that there is a comprehensive database of gene variants leading to OI: https://oi.gene.le.ac.uk/ . The list of OI genes is incomplete in Table 1. A comprehensive list of genes may be found at https://oi.gene.le.ac.uk/status.php . I have noted a few issues in this article: On page 2, in the section headed "Genes and classification", gene symbols ( COLIA1 and COL1A2 ) are inappropriately used to designate the component protein chains of type I collagen. Gene symbols and protein product names should not be used interchangeably. The protein chains are α1(I) and α2(I) respectively. In Table 1, the gene symbols for the mutant genes leading to OI types I, II, III and IV are incorrect. They should be COL1A1 and COL1A2 , not COL1A1 and COLA2 . In Table 1, the gene symbol for the gene encoding the protein prolyl-3 hydroxylase is P3H1 , not LEPRE1 . The gene symbol for this gene was changed to P3H1 in December 2014. Table 1 continues to propagate the notion that there are very many OI types when, in reality, there are really only five true types which can be clearly distinguished clinically (types I to V). The problem has been caused by several new OI types being created to correspond to newly discovered genes which harbour OI-causing sequence variants. This has only served to confuse matters and is discussed at length by Van Dijk and Sillence (2014) ( http://www.ncbi.nlm.nih.gov/pubmed/24715559 ). It is perhaps unsurprising that the article gives emphasis to pharmacological interventions for OI, given that one of the authors is employed by Alexion Pharmaceuticals, but it is improper to ignore surgical interventions such as rodding of long bones and mesenchymal stem cell therapy. There is no mention in the article of the fact that there is a comprehensive database of gene variants leading to OI: https://oi.gene.le.ac.uk/ . The list of OI genes is incomplete in Table 1. A comprehensive list of genes may be found at https://oi.gene.le.ac.uk/status.php . Competing Interests: I declare that I curate the database of OI gene variants which in mentioned in comment 6. Close Report a concern Comment ADD YOUR COMMENT Author details Author details 1 Endocrinology, Medical College of Wisconsin, Milwaukee, WI, USA 2 Orthopaedic and Rehabilitation Engineering Center, Marquette University and Medical College of Wisconsin, Milwaukee, WI, USA 3 Shriners Hospitals for Children, Chicago, IL, USA Competing interests JS is a consultant for Alexion Pharmaceuticals. The other authors declare that they have no competing interests. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (1) version 1 Published: 07 Sep 2015, 4:681 https://doi.org/10.12688/f1000research.6398.1 Copyright © 2015 Shaker JL et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Shaker JL, Albert C, Fritz J and Harris G. Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.12688/f1000research.6398.1 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 1 VERSION 1 PUBLISHED 07 Sep 2015 Views 0 Cite How to cite this report: Clarke B. Reviewer Report For: Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.5256/f1000research.6864.r10219 ) The direct URL for this report is: https://f1000research.com/articles/4-681/v1#referee-response-10219 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 07 Sep 2015 Bart Clarke , Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.6864.r10219 I confirm that I have read this submission and believe that I have an ... Continue reading READ ALL Competing Interests: No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Clarke B. Reviewer Report For: Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.5256/f1000research.6864.r10219 ) The direct URL for this report is: https://f1000research.com/articles/4-681/v1#referee-response-10219 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Rao SD. Reviewer Report For: Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.5256/f1000research.6864.r10218 ) The direct URL for this report is: https://f1000research.com/articles/4-681/v1#referee-response-10218 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 07 Sep 2015 Sudhaker Dhanwada Rao , Division of Endocrinology, Diabetes and Bone & Mineral Disorders, Henry Ford Hospital, Detroit, MI, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.6864.r10218 I confirm that I have read this submission and believe that I have an ... Continue reading READ ALL Competing Interests: No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Rao SD. Reviewer Report For: Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.5256/f1000research.6864.r10218 ) The direct URL for this report is: https://f1000research.com/articles/4-681/v1#referee-response-10218 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: McKenna MJ. Reviewer Report For: Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.5256/f1000research.6864.r10217 ) The direct URL for this report is: https://f1000research.com/articles/4-681/v1#referee-response-10217 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 07 Sep 2015 Malachi J. McKenna , St. Vincent's University Hospital, Dublin, Ireland Approved VIEWS 0 https://doi.org/10.5256/f1000research.6864.r10217 I confirm that I have read this submission and believe that I have an ... Continue reading READ ALL Competing Interests: No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT McKenna MJ. Reviewer Report For: Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.5256/f1000research.6864.r10217 ) The direct URL for this report is: https://f1000research.com/articles/4-681/v1#referee-response-10217 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Comments on this article Comments (1) Version 1 VERSION 1 PUBLISHED 07 Sep 2015 Reader Comment 01 Oct 2015 Raymond Dalgleish , University of Leicester, UK 01 Oct 2015 Reader Comment I have noted a few issues in this article: On page 2, in the section headed "Genes and classification", gene symbols ( COLIA1 and COL1A2 ) are inappropriately used to designate the component ... Continue reading I have noted a few issues in this article: On page 2, in the section headed "Genes and classification", gene symbols ( COLIA1 and COL1A2 ) are inappropriately used to designate the component protein chains of type I collagen. Gene symbols and protein product names should not be used interchangeably. The protein chains are α1(I) and α2(I) respectively. In Table 1, the gene symbols for the mutant genes leading to OI types I, II, III and IV are incorrect. They should be COL1A1 and COL1A2 , not COL1A1 and COLA2 . In Table 1, the gene symbol for the gene encoding the protein prolyl-3 hydroxylase is P3H1 , not LEPRE1 . The gene symbol for this gene was changed to P3H1 in December 2014. Table 1 continues to propagate the notion that there are very many OI types when, in reality, there are really only five true types which can be clearly distinguished clinically (types I to V). The problem has been caused by several new OI types being created to correspond to newly discovered genes which harbour OI-causing sequence variants. This has only served to confuse matters and is discussed at length by Van Dijk and Sillence (2014) ( http://www.ncbi.nlm.nih.gov/pubmed/24715559 ). It is perhaps unsurprising that the article gives emphasis to pharmacological interventions for OI, given that one of the authors is employed by Alexion Pharmaceuticals, but it is improper to ignore surgical interventions such as rodding of long bones and mesenchymal stem cell therapy. There is no mention in the article of the fact that there is a comprehensive database of gene variants leading to OI: https://oi.gene.le.ac.uk/ . The list of OI genes is incomplete in Table 1. A comprehensive list of genes may be found at https://oi.gene.le.ac.uk/status.php . I have noted a few issues in this article: On page 2, in the section headed "Genes and classification", gene symbols ( COLIA1 and COL1A2 ) are inappropriately used to designate the component protein chains of type I collagen. Gene symbols and protein product names should not be used interchangeably. The protein chains are α1(I) and α2(I) respectively. In Table 1, the gene symbols for the mutant genes leading to OI types I, II, III and IV are incorrect. They should be COL1A1 and COL1A2 , not COL1A1 and COLA2 . In Table 1, the gene symbol for the gene encoding the protein prolyl-3 hydroxylase is P3H1 , not LEPRE1 . The gene symbol for this gene was changed to P3H1 in December 2014. Table 1 continues to propagate the notion that there are very many OI types when, in reality, there are really only five true types which can be clearly distinguished clinically (types I to V). The problem has been caused by several new OI types being created to correspond to newly discovered genes which harbour OI-causing sequence variants. This has only served to confuse matters and is discussed at length by Van Dijk and Sillence (2014) ( http://www.ncbi.nlm.nih.gov/pubmed/24715559 ). It is perhaps unsurprising that the article gives emphasis to pharmacological interventions for OI, given that one of the authors is employed by Alexion Pharmaceuticals, but it is improper to ignore surgical interventions such as rodding of long bones and mesenchymal stem cell therapy. There is no mention in the article of the fact that there is a comprehensive database of gene variants leading to OI: https://oi.gene.le.ac.uk/ . The list of OI genes is incomplete in Table 1. A comprehensive list of genes may be found at https://oi.gene.le.ac.uk/status.php . Competing Interests: I declare that I curate the database of OI gene variants which in mentioned in comment 6. Close Report a concern Comment ADD YOUR COMMENT keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 1 07 Sep 15 read read read Malachi J. McKenna , St. Vincent's University Hospital, Dublin, Ireland Sudhaker Dhanwada Rao , Henry Ford Hospital, Detroit, USA Bart Clarke , Mayo Clinic College of Medicine, Rochester, USA Comments on this article All Comments (1) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2015 Clarke B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 07 Sep 2015 | for Version 1 Bart Clarke , Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Mayo Clinic College of Medicine, Rochester, MN, USA 0 Views copyright © 2015 Clarke B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Competing Interests No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Clarke B. Peer Review Report For: Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.5256/f1000research.6864.r10219) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/4-681/v1#referee-response-10219 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2015 Rao S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 07 Sep 2015 | for Version 1 Sudhaker Dhanwada Rao , Division of Endocrinology, Diabetes and Bone & Mineral Disorders, Henry Ford Hospital, Detroit, MI, USA 0 Views copyright © 2015 Rao S. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Competing Interests No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Rao SD. Peer Review Report For: Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.5256/f1000research.6864.r10218) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/4-681/v1#referee-response-10218 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2015 McKenna M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 07 Sep 2015 | for Version 1 Malachi J. McKenna , St. Vincent's University Hospital, Dublin, Ireland 0 Views copyright © 2015 McKenna M. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Competing Interests No competing interests were disclosed. Faculty Reviews are commissioned and written by members of the prestigious Faculty Opinions Faculty , and are edited as a service to our readers. In order to make these reviews as comprehensive and accessible as possible, we seek the reviewers’ input before publication. The reviewers’ names and any additional comments they may have are published alongside the review, as is usual on F1000Research. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) McKenna MJ. Peer Review Report For: Recent developments in osteogenesis imperfecta [version 1; peer review: 3 approved] . F1000Research 2015, 4 (F1000 Faculty Rev):681 ( https://doi.org/10.5256/f1000research.6864.r10217) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. 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