Comparison of Bone Microarchitecture Between Adult Osteogenesis Imperfecta and Early-Onset Osteoporosis

Rolvien, Tim; Stürznickel, Julian; Schmidt, Felix N.; Butscheidt, Sebastian; Schmidt, Tobias; Busse, Björn; Mundlos, Stefan; Schinke, Thorsten; Kornak, Uwe; Oheim, Ralf

doi:10.1007/s00223-018-0447-8

Cited by 37 publications

(27 citation statements)

References 33 publications

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“…For example, several groups have compared adults with osteogenesis imperfecta (OI) to apparently healthy subjects and showed severe trabecular deficits in radial and tibial parameters, especially in Tb.vBMD (−21% to −38.5%), Tb.N (−21.4% to −49.4%), and Tb.Sp. (+54.5% to +77.8%) . Although alterations were more severe in moderate–severe OI (type III/IV) than in mild OI (type I), the trabecular deterioration in all types of OI exceeded that observed in fracture subjects in the current study.…”

Section: Discussioncontrasting

confidence: 61%

“…(+54.5% to +77.8%). (64)(65)(66) Although alterations were more severe in moderate-severe OI (type III/IV) than in mild OI (type I), (65) the trabecular deterioration in all types of OI exceeded that observed in fracture subjects in the current study. Recently, Rolvien and colleagues used HR-pQCT to compare bone microarchitecture in adults with OI and sex-and agematched subjects with early-onset osteoporosis (EOOP; a condition distinct from postmenopausal osteoporosis in that it is characterized by low bone mass and the occurrence of fragility fractures before the age of 50 years) and healthy subjects.…”

Section: Hr-pqct and Bone Diseasescontrasting

confidence: 61%

“…In accordance with other publications, HR‐pQCT revealed significant differences in radial and tibial Tb.vBMD as well as in a number of bone geometry and microstructural parameters in the OI cohort compared with healthy subjects. The EOOP cohort also showed a number of significant differences compared with healthy subjects, but the pattern was somewhat different from that for the OI cohort …”

Section: Discussionmentioning

confidence: 73%

“…The EOOP cohort also showed a number of significant differences compared with healthy subjects, but the pattern was somewhat different from that for the OI cohort. (66) Together these studies suggest that pathological deficits in HR-pQCT bone parameters are at least the same if not larger than deficits associated with fracture in apparently healthy individuals and that HR-pQCT assessment may be valuable in longitudinally monitoring disease progression and treatment efficacy.…”

Section: Hr-pqct and Bone Diseasesmentioning

confidence: 83%

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HR-pQCT Measures of Bone Microarchitecture Predict Fracture: Systematic Review and Meta-Analysis

Mikolajewicz

Bishop

Burghardt

et al. 2019

Journal of Bone and Mineral Research

117

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High‐resolution peripheral quantitative computed tomography (HR‐pQCT) is a noninvasive imaging modality for assessing volumetric bone mineral density (vBMD) and microarchitecture of cancellous and cortical bone. The objective was to (1) assess fracture‐associated differences in HR‐pQCT bone parameters; and (2) to determine if HR‐pQCT is sufficiently precise to reliably detect these differences in individuals. We systematically identified 40 studies that used HR‐pQCT (39/40 used XtremeCT scanners) to assess 1291 to 3253 and 3389 to 10,687 individuals with and without fractures, respectively, ranging in age from 10.9 to 84.7 years with no comorbid conditions. Parameters describing radial and tibial bone density, microarchitecture, and strength were extracted and percentage differences between fracture and control subjects were estimated using a random effects meta‐analysis. An additional meta‐analysis of short‐term in vivo reproducibility of bone parameters assessed by XtremeCT was conducted to determine whether fracture‐associated differences exceeded the least significant change (LSC) required to discern measured differences from precision error. Radial and tibial HR‐pQCT parameters, including failure load, were significantly altered in fracture subjects, with differences ranging from −2.6% (95% confidence interval [CI] −3.4 to −1.9) in radial cortical vBMD to −12.6% (95% CI −15.0 to −10.3) in radial trabecular vBMD. Fracture‐associated differences reported by prospective studies were consistent with those from retrospective studies, indicating that HR‐pQCT can predict incident fracture. Assessment of study quality, heterogeneity, and publication biases verified the validity of these findings. Finally, we demonstrated that fracture‐associated deficits in total and trabecular vBMD and certain tibial cortical parameters can be reliably discerned from HR‐pQCT‐related precision error and can be used to detect fracture‐associated differences in individual patients. Although differences in other HR‐pQCT measures, including failure load, were significantly associated with fracture, improved reproducibility is needed to ensure reliable individual cross‐sectional screening and longitudinal monitoring. In conclusion, our study supports the use of HR‐pQCT in clinical fracture prediction. © 2019 American Society for Bone and Mineral Research.

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Section: Discussioncontrasting

confidence: 61%

Section: Hr-pqct and Bone Diseasescontrasting

confidence: 61%

Section: Discussionmentioning

confidence: 73%

Section: Hr-pqct and Bone Diseasesmentioning

confidence: 83%

See 2 more Smart Citations

HR-pQCT Measures of Bone Microarchitecture Predict Fracture: Systematic Review and Meta-Analysis

Mikolajewicz

Bishop

Burghardt

et al. 2019

Journal of Bone and Mineral Research

117

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“…Bei einigen dieser Per-sonen erfolgte ein "deep phenotyping" mithilfe der "high-resolution peripheral quantitative computed tomography" (HR-pQCT). Dabei konnten keine strukturellen Unterschiede zwischen Betroffenen mit Typ-1-Kollagenmutationen und EOOP-Patienten ohne Nachweis genetischer Ursachen identifiziert werden [28]. Die zweitgrößte EOOP-Subgruppe waren Patienten mit Mutationen in LRP5 oder WNT1, gefolgt von unerkannten Fällen von Hypophosphatasie durch ALPL-Mutationen und Mutationen im X-chromosomalen Gen PLS3.…”

Section: Monogenic Early-onset Osteoporosis and Senile Osteoporosis: unclassified

Monogene frühmanifeste Osteoporose und Altersosteoporose – ein Kontinuum

Kornak

Oheim

2019

Medizinische Genetik

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ZusammenfassungDas Risiko für atraumatische/osteoporotische Frakturen nimmt ab einem Alter von 55 Jahren zu und wird zu einem großen Teil durch die individuelle Knochenmineraldichte und -struktur bestimmt. Durch Modeling während des Wachstums und anschließendes Remodeling passen Osteoblasten und Osteoklasten als Teil der sog. „basic multicellular unit“ das Knochengewebe kontinuierlich an die Erfordernisse an. Angeborene Störungen ihrer Funktion und/oder ihres Zusammenspiels durch häufige oder seltene Genvarianten können durch verzögerten Knochenaufbau oder beschleunigten Knochenabbau zu einer pathologisch niedrigen Knochenmineraldichte (BMD) führen. Häufige Varianten in über 500 Genloci erklären zusammen derzeit ca. 20 % der BMD-Varianz und beeinflussen das Risiko der Altersosteoporose. In einem signifikanten Teil der erwachsenen Patienten mit frühmanifester Osteoporose (vor dem 55. Lebensjahr) finden sich hingegen seltene Varianten als monogene Krankheitsursache. Aufgrund der mitunter sehr milden und variablen Manifestation dieser monogenen Krankheiten ist die genetische Diagnostik die zuverlässigste Möglichkeit der molekularen Zuordnung. Die bei der früh- und spätmanifesten Osteoporose involvierten Gene zeigen eine deutliche Überlappung, besonders bei Genen mit Funktion im Wnt-Signalweg. Die Einbeziehung genetischer Varianten in den diagnostischen Prozess erlaubt eine genauere Prognose und möglicherweise auch eine spezifischere Therapie. Auf die Altersosteoporose lässt sich dieser personalisierte Ansatz unter Umständen in einem nächsten Schritt mithilfe polygener Risiko-Scores übertragen.

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Mice Carrying a Ubiquitous R235W Mutation of Wnt1 Display a Bone-Specific Phenotype

Yorgan

Rolvien

Stürznickel

et al. 2020

Journal of Bone and Mineral Research

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Since a key function of Wnt1 in brain development was established early on through the generation of non‐viable Wnt1‐deficient mice, it was initially surprising that WNT1 mutations were found to cause either early‐onset osteoporosis (EOOP) or osteogenesis imperfecta type XV (OI‐XV). The deduced function of Wnt1 as an osteoanabolic factor has been confirmed in various mouse models with bone‐specific inactivation or overexpression, but mice carrying disease‐causing Wnt1 mutations have not yet been described. Triggered by the clinical analysis of EOOP patients carrying a heterozygous WNT1 mutation (p.R235W), we introduced this mutation into the murine Wnt1 gene to address the question of whether this would cause a skeletal phenotype. We observed that Wnt1+/R235W and Wnt1R235W/R235W mice were born at the expected Mendelian ratio and that they did not display postnatal lethality or obvious nonskeletal phenotypes. At 12 weeks of age, the homozygous presence of the Wnt1 mutation was associated with reduced trabecular and cortical bone mass, explained by a lower bone formation rate compared with wild‐type littermates. At 52 weeks of age, we also observed a moderate bone mass reduction in heterozygous Wnt1+/R235W mice, thereby underscoring their value as a model of WNT1‐dependent EOOP. Importantly, when we treated wild‐type and Wnt1+/R235W mice by daily injection of parathyroid hormone (PTH), we detected the same osteoanabolic influence in both groups, together with an increased cortical thickness in the mutant mice. Our data demonstrate the pathogenicity of the WNT1‐R235W mutation, confirm that controlling skeletal integrity is the primary physiological function of Wnt1, and suggest that osteoanabolic treatment with teriparatide should be applicable for individuals with WNT1‐dependent EOOP. © 2020 American Society for Bone and Mineral Research.

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Comparison of Bone Microarchitecture Between Adult Osteogenesis Imperfecta and Early-Onset Osteoporosis

Cited by 37 publications

References 33 publications

HR-pQCT Measures of Bone Microarchitecture Predict Fracture: Systematic Review and Meta-Analysis

HR-pQCT Measures of Bone Microarchitecture Predict Fracture: Systematic Review and Meta-Analysis

Monogene frühmanifeste Osteoporose und Altersosteoporose – ein Kontinuum

Mice Carrying a Ubiquitous R235W Mutation of Wnt1 Display a Bone-Specific Phenotype

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