Diverging results of areal and volumetric bone mineral density in Down syndrome

García-Hoyos, M; García-Unzueta, Mayte; Luis, Daniel Antonio de; Valero, Carmen; Riancho, José A.

doi:10.1007/s00198-016-3814-1

Cited by 21 publications

(14 citation statements)

References 26 publications

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Section: Development Of Skeletal Abnormalities In Individuals With Dsmentioning

confidence: 99%

“…Although previous studies have long associated skeletal deficits with DS, it remains unclear how these alterations arise in individuals with Ts21 [1,[15][16][17][18][19]. Skeletal phenotypes associated with Ts21 are a consequence of impaired bone formation as exhibited by diminished bone accrual, early attainment of peak bone mass, abnormal mineralization, and low bone mineral density [1,2,[13][14][15]17,19,[21][22][23][24]. Men and women with DS displayed lower BMD in the femoral neck and lumbar spine much earlier than individuals without DS, with men exhibiting bone loss around 20 years of age, and females experience rapid decline in BMD around 40 years of age [6,7,14].…”

Section: Development Of Skeletal Abnormalities In Individuals With Dsmentioning

confidence: 99%

“…Increased average lifespan in individuals with DS [10][11][12] has made the development and advancement of bone disease a concern for older individuals with Ts21 [6][7][8]13,14]. Humans with DS and mouse models of DS exhibit sexual dimorphic features in skeletal anomalies that include age, severity, and skeletal compartment [1,[15][16][17][18][19][20].…”

Section: Introduction 1skeletal Abnormalities In Dsmentioning

confidence: 99%

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Skeletal Deficits in Male and Female down Syndrome Model Mice Arise Independent of Normalized Dyrk1a Expression in Osteoblasts

Thomas

Sloan

Cave

et al. 2021

Genes

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Trisomy 21 (Ts21) causes alterations in skeletal development resulting in decreased bone mass, shortened stature and weaker bones in individuals with Down syndrome (DS). There is a sexual dimorphism in bone mineral density (BMD) deficits associated with DS with males displaying earlier deficits than females. The relationships between causative trisomic genes, cellular mechanisms, and influence of sex in DS skeletal abnormalities remain unknown. One hypothesis is that the low bone turnover phenotype observed in DS results from attenuated osteoblast function, contributing to impaired trabecular architecture, altered cortical geometry, and decreased mineralization. DYRK1A, found in three copies in humans with DS, Ts65Dn, and Dp1Tyb DS model mice, has been implicated in the development of postnatal skeletal phenotypes associated with DS. Reduced copy number of Dyrk1a to euploid levels from conception in an otherwise trisomic Ts65Dn mice resulted in a rescue of appendicular bone deficits, suggesting DYRK1A contributes to skeletal development and homeostasis. We hypothesized that reduction of Dyrk1a copy number in trisomic osteoblasts would improve cellular function and resultant skeletal structural anomalies in trisomic mice. Female mice with a floxed Dyrk1a gene (Ts65Dn,Dyrk1afl/wt) were mated with male Osx-Cre+ (expressed in osteoblasts beginning around E13.5) mice, resulting in reduced Dyrk1a copy number in mature osteoblasts in Ts65Dn,Dyrk1a+/+/Osx-Cre P42 male and female trisomic and euploid mice, compared with littermate controls. Male and female Ts65Dn,Dyrk1a+/+/+ (3 copies of DYRK1A in osteoblasts) and Ts65Dn,Dyrk1a+/+/Osx-Cre (2 copies of Dyrk1a in osteoblasts) displayed similar defects in both trabecular architecture and cortical geometry, with no improvements with reduced Dyrk1a in osteoblasts. This suggests that trisomic DYRK1A does not affect osteoblast function in a cell-autonomous manner at or before P42. Although male Dp1Tyb and Ts65Dn mice exhibit similar skeletal deficits at P42 in both trabecular and cortical bone compartments between euploid and trisomic mice, female Ts65Dn mice exhibit significant cortical and trabecular deficits at P42, in contrast to an absence of genotype effect in female Dp1Tyb mice in trabecular bone. Taken together, these data suggest skeletal deficits in DS mouse models and are sex and age dependent, and influenced by strain effects, but are not solely caused by the overexpression of Dyrk1a in osteoblasts. Identifying molecular and cellular mechanisms, disrupted by gene dosage imbalance, that are involved in the development of skeletal phenotypes associated with DS could help to design therapies to rescue skeletal deficiencies seen in DS.

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Section: Development Of Skeletal Abnormalities In Individuals With Dsmentioning

confidence: 99%

Section: Development Of Skeletal Abnormalities In Individuals With Dsmentioning

confidence: 99%

Section: Introduction 1skeletal Abnormalities In Dsmentioning

confidence: 99%

See 1 more Smart Citation

Skeletal Deficits in Male and Female down Syndrome Model Mice Arise Independent of Normalized Dyrk1a Expression in Osteoblasts

Thomas

Sloan

Cave

et al. 2021

Genes

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“…Zur Detektion der Osteoporose bei Menschen mit geistiger Behinderung ist möglicherweise die DXA-Messung an Hüfte oder Lendenwirbelsäule weniger effektiv als bei Menschen ohne geistige Behinderung. Bei Menschen mit Trisomie 21 war beispielsweise eine volumetrische Messung ("volumetric BMD") der üblichen Knochendichtemessung in der Fläche ("areal BMD") überlegen [16], [17]. Die Anwendung von quantitativen Ultraschallverfahren ist in der DVO-Leitlinie von 2017 nur eingeschränkt und nicht als Routinescreeningmethode empfohlen [18] kann jedoch bei Menschen mit geistiger Behinderung unter anderem aufgrund des geringen Untersuchungsaufwandes von Vorteil sein [3].…”

Section: Screening Auf Osteoporose Bei Menschen Mit Geistiger Behindeunclassified

Osteoporose/Frakturen bei Menschen mit geistiger Behinderung

2019

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ZusammenfassungOsteoporose und Frakturen treten bei Menschen mit geistiger Behinderung häufig auf, werden aber dafür zu selten diagnostiziert. Die Ursachen für das erhöhte Risiko einer Osteoporose und die ebenfalls erhöhte Sturzrate sind vielfältig. Immobilität, verminderte Sonnenlichtexposition, hormonelle Störungen zum Beispiel im Rahmen eines Hypogonadismus, antiepileptische und antipsychotische Medikamente und aus der Behinderung folgende Balanceprobleme gehören dazu. Die Diagnostik von Osteoporose und Frakturen kann bei Menschen mit geistiger Behinderung erschwert sein. Einschränkungen in der Kommunikation erhöhen die Gefahr, Frakturen verzögert zu diagnostizieren oder gar zu übersehen. Ein frühes Screening auf Osteoporose, die Berücksichtigung von Risikofaktoren und eine individuelle Behandlung der Osteoporose sind notwendig. Gleichzeitig sind Sturzpräventionsmaßnahmen wie z. B. körperliches Training oder eine Anpassung der Umgebung sinnvoll.

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“…The calculation of volumetric BMD (BMD VOL ) may be more appropriate to compare achondroplasic BMD to controls as it takes into account a greater amount of the observed bone. For example, in shorter statured groups, BMD is lower than taller groups but similar when presented as BMD VOL [18, 19]. It would therefore be more useful to describe the BMD VOL , such as the lumbar vertebra, of achondroplasic groups to provide a more accurate representation of BMD compared to controls.…”

Section: Introductionmentioning

confidence: 99%

Whole-body and segmental analysis of body composition in adult males with achondroplasia using dual X-ray absorptiometry

et al. 2019

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Achondroplasia is a condition characterized by a genetic mutation affecting long bone endplate development. Current data suggests that the bone mineral content (BMC) and bone mineral density (BMD) of achondroplasic populations are below age matched individuals of average stature (controls). Due to the disproportionate limb-to-torso length compared to controls however, the lower BMC and BMD may be nullified when appropriately presented. The aim of this study was to measure whole-body and segmental body composition in adult males with achondroplasia (N = 10, 22 ±3 yrs), present data relative to whole-body and whole-limb values and compare all values to age matched controls (N = 17, 22 ±2 yrs). Dual X-ray absorptiometry (DEXA) was used to measure the in vivo mass of the whole-body and 15 segments, from which BMD, BMC, fat free mass (FFM) and body fat mass were measured. BMC of lumbar vertebrae (L1-4) was also measured and presented as a volumetric BMD (BMDVOL). The achondroplasic group had less BMC, BMD and FFM, and more body fat mass than controls as a whole-body measure. The lower achondroplasic BMC and BMD was somewhat nullified when presented relative to whole-body and whole-limb values respectively. There was no difference in lumbar BMDVOL between groups. Whole-body BMD measures presented the achondroplasic group as ‘osteopenic’. When relative to whole-limb measures however, achondroplasic BMD descriptions were normal. Further work is needed to create a body composition database for achondroplasic population’s, or for clinicians to present achondroplasic body composition values relative to the whole-limb.

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Diverging results of areal and volumetric bone mineral density in Down syndrome

Abstract: Areal BMD is reduced in DS, but it seems to be related to the smaller body and skeletal size. In fact, the estimated volumetric BMD is similar in patients with DS and in control individuals. Furthermore, people with DS have normal bone microarchitecture.

Cited by 21 publications

References 26 publications

Skeletal Deficits in Male and Female down Syndrome Model Mice Arise Independent of Normalized Dyrk1a Expression in Osteoblasts

Skeletal Deficits in Male and Female down Syndrome Model Mice Arise Independent of Normalized Dyrk1a Expression in Osteoblasts

Osteoporose/Frakturen bei Menschen mit geistiger Behinderung

Whole-body and segmental analysis of body composition in adult males with achondroplasia using dual X-ray absorptiometry

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