Bone Mineral Density Distribution Curves in Spanish Adults With Down Syndrome

doi:10.1016/j.jocd.2018.03.001

Journal of Clinical Densitometry

Volume 21, Issue 4, October–December 2018, Pages 493-500

https://doi.org/10.1016/j.jocd.2018.03.001 Get rights and content

Abstract

According to reports from small-sized case series, adults with Down syndrome (DS) appear to have lower bone mineral density (BMD) than the general population. The objective of our study was to further characterize the bone mass acquisition curve in an adult DS population. This is a retrospective study of 297 adults with DS from the Adult Down Syndrome Outpatient Clinic of a tertiary care hospital in Madrid, Spain, who underwent a bone densitometry (Hologic QDR-4500W), for clinical purposes between January 2010 and June 2015. The mean age of our sample population was 34 yr (±10.9); 51% were women. Bone mass peak was reached earlier and was lower than the general population (around 20–25 yr), with almost parallel curves. The mean BMD was 0.715 ± 0.12 g/cm² in femoral neck (FN) and 0.872 ± 0.11 g/cm² in lumbar spine (LS). According to FN scores, 52% of the subjects were classified as osteopenic and 18% as osteoporotic. According to LS scores, frequencies were 54% and 25%, respectively. BMD was considered inadequate for the age (Z-score < −2 standard deviation) in 18% of the subjects at FN and 40% at LS. BMD at LS was significantly lower in males than in females (52% vs 38%, p < 0.001). Male DS subjects had a 2.58-fold (95% confidence interval: 1.57–4.25) higher risk of developing reduced BMD at LS than females. Persons with DS reach the bone mass peak earlier and this bone mass is lower than the general population. Among subjects with DS, male gender is a risk factor for developing low BMD, especially at LS.

Introduction

Down syndrome (DS) is the most frequent chromosomal disorder in live newborns and the first cause of congenital intellectual disability in Western countries (1). Its incidence ranges from 1/660 to 1/1000 newborns 2, 3. Increased survival of children with DS since the 1980s has resulted in a greater lifespan for this population (4). Significant medical advances such as improvement in cardiac surgery, prevention of childhood infections, broader access to standard care, and better global psychosocial support for persons with DS, have enabled adults with DS to reach the seventh decade of life (5). In fact, the lifespan of adults with DS could be similar to that of the general population within the next generation (6). This “new” population of adults with DS poses unique clinical problems that differ from those of the pediatric population with DS or the general population (6). Progressive aging is causing a shift in care to adults with DS, with special attention to specific aging-related health areas, such as the study of alterations in bone metabolism (7).

Osteoporosis is a growing public health problem, characterized by decreased bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture, especially of the hip, spine, and wrist (8). In Europe, more than 12 million postmenopausal women have osteoporosis. Furthermore, osteoporosis in Europe is responsible for 2.7 million fractures a year, representing an annual cost of €38.7 billion (9), being one of the main causes of functional decline, institutionalization, and dependence, especially in aging people. About 80% of these individuals are women, most of whom are over 50 yr. The prevalence of osteoporosis in Spain ranges between 25% in women aged 60–69 yr and 40% in those aged 70–79 yr (10).

DS has been proposed as an independent risk factor for the development of osteopenia and osteoporosis (11). Diverse studies have revealed altered bone mass in children and adolescents with DS, whose bone composition differs from that of the general population regarding its biomechanical resistance to fractures 12, 13. Preliminary studies described lower bone mineral density (BMD) in adults with DS compared with the general population, after adjusting for age and gender 14, 15, 16. This difference may be caused by an anomalous bone formation during childhood and puberty, leading to a reduced bone turnover and mineralization (11). In addition, a higher incidence of falls has also been observed in adults with DS (17).

However, this preliminary information comes from small-sized studies, making it difficult to extrapolate these results to the global population with DS, or to generalize curves of bone mass acquisition. Díaz Curiel et al (18) generated standard curves of BMD for the Spanish population using dual-energy X-ray absorptiometry (DXA), with 2442 subjects of both sexes aged 20–80 yr (i.e., 6 × 10⁻⁵ of Spanish population). The principal aim of our study was to generate a standard BMD curve for Spanish DS population using DXA, with 297 DS subjects of both sexes aged 15–64 yr (i.e., 9 × 10⁻³ of Spanish DS population). Other objectives of this study were to evaluate the prevalence of osteopenia and osteoporosis in the Spanish DS population and to compare the curves of BMD accrual of the Spanish DS population with the curves of the Spanish general population.

Section snippets

Study Design

This is a descriptive retrospective study of 297 adults with DS, consecutively sampled from patients attending the Adult Down Syndrome Outpatient Clinic of the Department of Internal Medicine, at Hospital Universitario de La Princesa, Madrid, Spain. The recruitment period was extended from January 2010 to June 2015. The study was conducted in accordance with the provisions of the Declaration of Helsinki and the 2013 Good Clinical Practice guidelines. The local institutional review board

Clinical and Anthropometric Characteristics

The study sample comprised 297 adults with DS. The gender distribution was uniform, 145 males (49%) vs 152 females (51%), and the mean age was 34.3 ± 11 yr. Age distribution in the 10-yr groups (from 15 to 64 yr) divided by gender is depicted in Table 1. Table 2 shows the anthropometrics and DXA characteristics of our DS population. Of note, females had a greater BMI than males (28.7 ± 5.6 vs 26.8 ± 4.7, p = 0.002), with higher rates of obesity.

Densitometric Characteristics

Summarized results of the densitometric evaluation

Discussion

To the best of our knowledge, this study evaluating BMD by DXA includes the largest population of DS subjects studied to date. In this study, we describe the evolution curves of BMD in persons with DS according to age. Indeed, the distribution curve of bone mass is quite similar to that of the general population, although BMD values are significantly lower in DS. In the general Spanish population, the bone mass peak is usually reached around 25–30 yr of age. By contrast, we have found that in

Conclusions

In our study, subjects with DS have lower areal BMD than the general Spanish population, especially DS males at LS, which could be considered as a new risk group of low BMD. However, we do not know whether this low BMD correlates with a higher incidence of vertebral fractures.

Interestingly, the distribution of bone mass curves is similar between DS and Spanish general population, although BMD and the peak of bone mass are significantly lower and achieved at an earlier age in DS. Our curves

Acknowledgments

The authors thank Eugenio Escolano, DXA technician, for his invaluable support in DXA measurements and Dr. Manuel Gómez Gutiérrez for his kind review of the final draft of the manuscript.

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Cited by (15)

Compromised femoral and lumbovertebral bone in the Dp(16)1Yey Down syndrome mouse model
2024, Bone
Down syndrome (DS), affecting ∼1 in 800 live births, is caused by the triplication of human chromosome 21 (Hsa21). Individuals with DS have skeletal features including craniofacial abnormalities and decreased bone mineral density (BMD). Lowered BMD can lead to increased fracture risk, with common fracture points at the femoral neck and lumbar spine. While the femur has been studied in DS mouse models, there is little research done on the vertebrae despite evidence that humans with DS have affected vertebrae. Additionally, it is important to establish when skeletal deficits occur to find times of potential intervention. The Dp(16)1Yey DS mouse model has all genes triplicated on mouse chromosome 16 orthologous to Hsa21 and displayed deficits in long bone, including trabecular and cortical deficits in male but not female mice, at 12 weeks. We hypothesized that the long bone and lumbovertebral microarchitecture would exhibit sexually dimorphic deficits in Dp(16)1Yey mice compared to control mice and long bone strength would be diminished in Dp(16)1Yey mice at 6 weeks. The trabecular region of the 4th lumbar (L4) vertebra and the trabecular and cortical regions of the femur were analyzed via micro-computed tomography and 3-point bending in 6-week-old male and female Dp(16)1Yey and control mice. Trabecular and cortical deficits were observed in femurs from male Dp(16)1Yey mice, and cortical deficits were seen in femurs of male and female Dp(16)1Yey mice. Male Dp(16)1Yey femurs had more deficits in bone strength at whole bone and tissue-estimate level properties, but female Dp(16)1Yey mice were also affected. Additionally, the L4 of male and female Dp(16)1Yey mice show trabecular deficits, which have not been previously reported in a DS mouse model. Our results indicate that skeletal deficits associated with DS occur early in skeletal development, are dependent on skeletal compartment and site, are sex dependent, and potential interventions should likely begin early in skeletal development of DS mouse models.
Low bone mass and impaired fracture healing in mouse models of Trisomy21 (Down syndrome)
2022, Bone
Individuals with Down syndrome (DS), the result of trisomy of human chromosome Hsa21 (Ts21), present with an array of skeletal abnormalities typified by altered craniofacial features, short stature and low bone mineral density (BMD). While bone deficits progress with age in both sexes, low bone mass is more pronounced in DS men than women and osteopenia appears earlier. In the current study, the reproductive hormone status (FSH, LH, testosterone) of 17 DS patients (males, ages range 19–52 years) was measured. Although testosterone was consistently low, the hypothalamic-pituitary-gonadal axis was intact with corresponding rises in FSH and LH. To provide further insight into the heterogeneity of the bone mass in DS, the skeletal phenotypes of three of the most used murine DS models, Ts65Dn (Ts65), TC1, and Dp16(Yey1) (Dp16) were characterized and contrasted. Evaluation of the bone phenotype of both male and female 3-month-old Dp16 mice demonstrated sexual dimorphism, with low bone mass apparent in males, as it is in Ts65, but not in female Dp16. In contrast, male TC1 mice had no apparent bone phenotype. To determine whether low bone mass in DS impacted fracture healing, fractures of the middle phalanx (P2) digits were generated in both male and female Dp16 mice at 15 weeks of age, an age where the sexually dimorphic low BMD persisted. Fracture healing was assessed via in vivo microCT over (13 weeks) 93 days post fracture (DPF). At 93 DPF, 0 % of DS male (n = 12) or female (n = 8) fractures healed, compared to 50 % of the male (n = 28) or female (n = 8) WT littermate fractures. MicroCT revealed periosteal unbridged mineralized callus formation across the fracture gap in Dp16 mice, which was confirmed by subsequent histology. These studies provide the first direct evidence of significantly impaired fracture healing in the setting of DS.
Kidney-vascular-bone axis in down syndrome
2022, Nefrologia
Citation Excerpt :
It should be remembered that bone formation occurs early in life. This temporal aspect has been valued by some authors, showing that subjects with DS present an early and less pronounced bone mass peak as compared with the general population.22 .
Volumetric BMD by 3D-DXA and Trabecular Bone Score in Adults With Down Syndrome
2021, Journal of Clinical Densitometry
Citation Excerpt :
All subjects underwent a DXA evaluation using a densitometer Hologic QDR-4500W (model Elite, S/N 50014, Bedford, MA). In our experience, the in vivo coefficients of variation for total hip (TH) and LS measurements are 1.3% and 0.5%, respectively (23). Osteoporosis and osteopenia were defined following internationally accepted criteria using the T and Z-scores (25).
Adults with Down syndrome (DS) have lower bone mineral density (BMD) than the general population. The objective of our study was to describe bone mineral status in DS population through volumetric BMD (vBMD) and trabecular bone score (TBS). Retrospective study of 297 subjects recruited from the Adult DS Outpatient Clinic of a tertiary care hospital in Spain, who underwent a bone densitometry for clinical purposes between January 2010 and June 2015. vBMD determination and TBS analysis on conventional DXA (Hologic QDR 4500) densitometer were performed in this cohort. The mean (±SD) age of our population was 34.3 (±10.9) years; 51% were women. Trabecular vBMD at total hip and femoral neck was lower in males than in females (191.7 ± 48.4 mg/cm³ vs 206.9 ± 46.7 mg/cm³, p = 0.007, and 250.5 ± 70.1 mg/cm³ vs 275.7 ± 66.2 mg/cm³, p = 0.002, respectively). Trabecular and cortical vBMD decreased with age, but age decline in trabecular vBMD was more pronounced in males. Likewise, lumbar TBS declined with age being normal in 63%, low in 29% and very low in 8% of subjects with DS, without differences between sexes. TBS showed a positive correlation (r = 0.37; p < 0.001, Kappa index= 0.275) with conventional DXA lumbar Z-score. vBMD at the hip showed lower values in DS subjects than in the general population, especially in males. Moreover, TBS was also lower at lumbar spine. Therefore, both assessments could be used as complementary tools to areal BMD (Z-score) to assess bone status in DS subjects.
Interaction of sexual dimorphism and gene dosage imbalance in skeletal deficits associated with Down syndrome
2020, Bone
All individuals with Down syndrome (DS), which results from trisomy of human chromosome 21 (Ts21), present with skeletal abnormalities typified by craniofacial features, short stature and low bone mineral density (BMD). Differences in skeletal deficits between males and females with DS suggest a sexual dimorphism in how trisomy affects bone. Dp1Tyb mice contain three copies of all of the genes on mouse chromosome 16 that are homologous to human chromosome 21, males and females are fertile, and therefore are an excellent model to test the hypothesis that gene dosage influences the sexual dimorphism of bone abnormalities in DS. Dp1Tyb as compared to control littermate mice at time points associated with bone accrual (6 weeks) and skeletal maturity (16 weeks) showed deficits in BMD and trabecular architecture that occur largely through interactions between sex and genotype and resulted in lower percent bone volume in all female and Dp1Tyb male mice. Cortical bone in Dp1Tyb as compared to control mice exhibited different changes over time influenced by sex × genotype interactions including reduced cortical area in both male and female Dp1Tyb mice. Mechanical testing analyses suggested deficits in whole bone properties such as bone mass and geometry, but improved material properties in female and Dp1Tyb mice. Sexual dimorphisms and the influence of trisomic gene dosage differentially altered cellular properties of male and female Dp1Tyb bone. These data establish sex, gene dosage, skeletal site and age as important factors in skeletal development of DS model mice, paving the way for identification of the causal dosage-sensitive genes. Skeletal differences in developing male and female Dp1Tyb DS model mice replicated differences in less-studied adolescents with DS and established a foundation to understand the etiology of trisomic bone deficits.
Skeletal dynamics of Down syndrome: A developing perspective
2020, Bone
Citation Excerpt :
Peak mass of the appendicular skeleton in the general population is normally attained near the end of the second decade of life but may be reached as early as 18 and as late as 35 years of age [44]. Individuals with DS reach peak bone mass 5–10 years earlier than the general population [19]. Hypogonadism is a common feature of DS, but more common in males than females.
Individuals with Down syndrome (DS) display distinctive skeletal morphology compared to the general population, but disparate descriptions, methodologies, analyses, and populations sampled have led to diverging conclusions about this unique skeletal phenotype. As individuals with DS are living longer, they may be at a higher risk of aging disorders such as osteoporosis and increased fracture risk. Sexual dimorphism has been suggested between males and females with DS in which males, not females, experience an earlier decline in bone mineral density (BMD). Unfortunately, studies focusing on skeletal health related to Trisomy 21 (Ts21) are few in number and often too underpowered to answer questions about skeletal development, resultant osteoporosis, and sexual dimorphism, especially in stages of bone accrual. Further confounding the field are the varied methods of bone imaging, analysis, and data interpretation. This review takes a critical look at the current knowledge of DS skeletal phenotypes, both from human and mouse studies, and presents knowledge gaps that need to be addressed, differences in research methodologies and analyses that affect the interpretation of results, and proposes guidelines for overcoming obstacles to understand skeletal traits associated with DS. By examining our current knowledge of bone in individuals with Ts21, a trajectory for future studies may be established to provide meaningful solutions for understanding the development of and improving skeletal structures in individuals with and without DS.

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: Conflicts of interest: The authors have no conflicts of interest to disclose. Part of this study was presented as an oral communication at the 4th Iberoamerican Down Syndrome Congress, Salamanca, Spain, March 16–18, 2016.

: Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

^a: S. Castañeda and F. Moldenhauer share senior authorship.

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Original ArticleBone Mineral Density Distribution Curves in Spanish Adults With Down Syndrome

Abstract

Introduction

Section snippets

Study Design

Clinical and Anthropometric Characteristics

Densitometric Characteristics

Discussion

Conclusions

Acknowledgments

Lancet

Lancet

Med Clin (Barc)

Endocr Pract

Eur J Obstet Gynecol Reprod Biol

Síndrome de Down

A population-based evaluation of the impact of antenatal screening for Down's syndrome in France, 1981–2000

BJOG

Clinical, social, and ethical implications of changing life expectancy in Down syndrome

Dev Med Child Neurol

Medical conditions and medication use in adults with Down syndrome: a descriptive analysis

Downs Syndr Res Pract

Endocrine and musculoskeletal abnormalities in patients with Down syndrome

Nat Rev Endocrinol

Consensus development conference: diagnosis, prophylaxis, and treatment of osteoporosis

Am J Med

Osteoporos Int

Original Article
Bone Mineral Density Distribution Curves in Spanish Adults With Down Syndrome