Full text of DOI:10.1007/s00223001093

Calcif Tissue Int (2000) 67:37–40
DOI: 10.1007/s00223001093
© 2000 Springer-Verlag New York Inc.
Ultrasonographic, Axial, and Peripheral Measurements in Female
Patients with Benign Hypermobility Syndrome
J. Nijs, E. Van Essche, M. De Munck, J. Dequeker
Arthritis and Metabolic Bone Disease Research Unit, K.U. Leuven, U.Z. Pellenberg, Weligerveld 1,B-3212 Pellenberg, Belgium
Received: 8 May 1999 / Accepted: 21 January 2000
Materials and Methods
Abstract. Twenty-five female Caucasians, aged 19–57
years, with the hypermobility syndrome had bone density
measurements using established noninvasive techniques
such as dual X-ray absorptiometry (DXA), single photon
absorptiometry (SPA), heel ultrasound (US), and peripheral
computed tomography (pQCT) acquisitions of the radius.
As a group, comparisons of the different bone indices with
the corresponding age-matched reference population re-
sulted in normal z-scores for the arial densities, however,
values for the volumetric total and cortical bone at the ra-
dius measured by pQCT were significantly lower than ex-
pected (P < 0.0001). Spinal and femoral bone density results
were significant after correction for body mass index (BMI).
This cross-sectional study shows that the benign hypermo-
bility syndrome patients have lowered t-scores for data re-
flecting bone structure and bone strength as measured with
US and the tomographic technique.
Subjects
Twenty-five Caucasian women diagnosed with benign hypermo-
bility syndrome by the Beighton score were seen in our rheuma-
tology unit at the University of Leuven. Their ages ranged from 19
to 57 years and only three were older than 50 years. Four of the
younger group had body mass index (BMI) values of >26, indi-
cating obesity. All subjects completed a standardized, extensive
questionnaire about risk for osteoporosis [4]. None were on hor-
monal replacement therapy nor bone active medications. After
giving informed consent they were enrolled in this study.
Study Design
Single photon absorptiometry (SPA) measurements were done in
the cortical bone region of the nondominant radius [5] with a SP2
densitometer (Lunar, Madison, WI, USA) providing projected
bone density values. All patients also had spinal, proximal femur,
and total body acquisitions at the same moment obtained with the
dual X-ray absorptiometry (DXA) technique [6] using a DPX-L
system (Lunar). Bone density data of the regions L2–L4, femoral
neck, and total skeleton were evaluated.
Key words: Hypermobility syndrome — Bone density —
pQCT — Heel ultrasound — Fracture risk.
Peripheral quantitative computed tomography (pQCT) mea-
surements were done at the ultradistal nondominant radius with the
XCT960 machine (Stratec); a technical description and precision
data of this technique are available [7]. Volumetric bone density
values were obtained for total cortical and trabecular bone in a
region located 4% proximal to the ulnar styloid, and a biomechan-
ical estimate of the resistance to bending [8], so-called strength
strain index (SSI), was calculated by software version 5.2. The
female controls (n ס 40) had a mean BMD of 22.1 ± 3. Quanti-
tative ultrasound data (QUS) were also obtained using the Achilles
plus system [9], evaluating the stiffness index which represents a
combination of speed of sound and broadband ultrasound attenu-
ation results [10].
The benign hypermobility syndrome has been defined as an
affliction with musculoskeletal symptoms in the absence of
the systemic rheumatological disease [1]. Hypermobility
due to joint laxity is also seen in other hereditary connective
tissue diseases such as osteogenesis imperfecta. The gener-
ally accepted method of assessing joint hypermobility is by
scoring the patient by Beighton’s criteria [2] where the
maximum score of 9 denotes maximum joint laxity. The
presence of arthralgia, traumatic or overused soft tissue le-
sions, joint dislocation, or subluxation are known events, as
well as cardiovascular, skin, and bone abnormalities [3].
The purpose of this study was to evaluate if, in the be-
nign hypermobility syndrome, the bone density alterations
predispose these patients to osteoporotic fractures. The pa-
tients have been seen in our rheumatology unit and all had
bone density measurements using different techniques such
as dual X-ray absorptiometry (DXA), single photon absorp-
tiometry (SPA), ultrasound (US), and peripheral quantita-
tive computed tomography (pQCT). To our knowledge this
is the first systematic study investigating bone density, si-
multaneously obtained with four different noninvasive tech-
niques, in different anatomical regions.
Statistics
The patients were ranked to normality by comparing the different
Table 1. Descriptive variables
Mean ± SD
Age (years)
Height (cm)
Weight (kg)
BMI
41.2 ± 10
166 ± 6
65 ± 18
23.4 ± 6
4.6 ± 2
Beighton score
Correspondence to: J. Nijs

38
J. Nijs et al.: Measurements of Females with Benign Hypermobility
Table 2. Mean ± SD of the z- and t-scores with P values
z
t
Mean ± SD
P
Mean ± SD
P
Lumbar L2–L4
Femur neck
Total body
Radius 1/3
pQCT total
pQCT trabecular
pQCT cortical
ppQCT SSI
SOS calcaneus
BUA
0.13 ± 1.3
−0.09 ± 1.3
0.34 ± 0.8
−0.05 ± 1.5
−0.48 ± 0.6
−0.04 ± 0.7
−0.60 ± 0.7
−0.44 ± 1.0
−0.23 ± 1.3
−0.41 ± 1.4
0.17 ± 1
−0.73 ± 1.5
−0.72 ± 0.4
−0.64 ± 0.5
−0.79 ± 0.7
−0.60 ± 0.9
−0.71 ± 0.9
−0.26 ± 1.1
−0.60 ± 1.3
<0.025
<0.0001
<0.0001
<0.0001
<0.01
<0.002
<0.001
<0.05
<0.001
Stiffness
0.42 ± 1.3
<0.05
Table 3. Mean ± SD of the skeletal size parameters with P values
Mean SD
Hypermobility
Normals
P
Radial width
Lumbar area
Neck area
1.301 ± 0.13
43.43 ± 4.38
4.98 ± 0.52
1.258 ± 0.09
40.10 ± 3.24
4.53 ± 0.44
<0.01
<0.005
Total body area
2147
± 199
2118
± 222
bone indices with the corresponding reference population and ex-
pressing the results in z-scores and t-scores, respectively, depend-
ing on age-matched controls or comparisons to the peak bone
value [11]. One sample test statistic was used to check for signifi-
cances concerning comparisons to normality [12] for the complete
group of subjects, with 5% as level of significance.
pared with data obtained in 19 age-matched female controls
(Table 3).
The questionnaire resulted in the following answers, re-
flecting the symptoms of the disease: 68% of the patients
reported the presence of acute inflammations mainly in the
hip, shoulders, or wrist. Sixteen percent of the subjects had
been immobilized, and 52% reported absenteeism (from
work/school) because of the disease. Positive skin elasticity
was reported by all of the patients and only one developed
mitral valve prolapse.
Results
The mean (±SD) values of the descriptive variables for the
studied individuals show a mean Beighton score of 4.6 with
a range of 1–8 (Table 1). Comparisons of the different bone
indices (Table 2), obtained with the different techniques, to
the corresponding reference data are presented as z-scores in
relation to age-matched controls. The DXA, SPA, and heel
US values were within normal limits for the axial as well as
for the total skeleton.
In contrast, significant reductions were found for the
volumetric total and cortical bone density values measured
by pQCT as well as for the estimated bone strength param-
eter (SSI). The diagnostic sensitivity, presented as t-scores,
was normal for the DXA measurements and statistical sig-
nificant losses were observed for all radial pQCT acquisi-
tions. Significant reduced data were also obtained for the
US parameters. These results are independent of the hor-
monal state because 25% of these women were postmeno-
pausal and 16% had no children. Lactation in 42% of the
patients is also no determinating factor but the size of the
studied group is limited. Correcting for body mass index
(BMI) the lumbar spine and proximal femur data also be-
come significant in terms of diagnostic sensitivity with t-
scores of −.052 ± 1 and −0.63 ± 1.3, respectively (P < 0.05).
The different skeletal size parameters obtained with the
single and dual energy techniques show elevated skeletal
dimensions in the group with hypermobility syndrome com-
Discussion
Generalized joint hypermobility is a feature of inherited
disorders of connective tissue such as osteogenesis imper-
fecta, Marfan syndrome, and Ehlers-Danlos syndrome [13].
It has been shown that patients with a mild degree of os-
teogenesis imperfecta suffer from significant bone deficits
in the lumbar spine as well as in the femoral neck even after
correction for the lower body weight of the patients [14].
Conflicting bone density results can be found in patients
with the Marfan syndrome claiming the association with
osteoporosis [15] and other investigators found normal bone
density [16]. This study evaluates the bone status of patients
with the hypermobility syndrome, as diagnosed by the
Beighton criteria, excluding the Ehlers-Danlos syndrome as
well as the Marfan syndrome [17] with results using differ-
ent noninvasive techniques. Single photon and DXA sys-
tems provide areal density results but fail correction for
bone size, leading to the erroneous view that areal bone
density increases with aging during growth [18, 19]. Evalu-
ating the volumetric density data, obtained with QCT, the
amount of bone in the enlarging bone is constant [20].
Knowing that bone size or cross-sectional area is an
independent determinant of bone strength [21], investiga-

J. Nijs et al.: Measurements of Females with Benign Hypermobility
39
tions of bone structure and geometry need more attention.
Cortical surface, cortical thickness, and assessment of bone
strength can be analyzed by newer computerized tomo-
graphic methods [22]. Table 4 gives an overview, as can be
found in the literature, of the findings on the bone status of
the different inherited disorders of connective tissue com-
pared with controls for the different available noninvasive
techniques.
Our results in benign hypermobility confirm the results
of Mishra et al. [3] who also found a tendency to lower
DXA spine and hip values, but our study indicates that
geometrical factors increased bone densities, explaining
why the volumetric density at the radius is reduced in these
cases. Compared with diseases related to benign hypermo-
bility such as Ehlers Danlos [23, 24], osteogenesis imper-
fecta [14, 25] and Marfan [27, 28] low bone density in
benign hypermobility is much less. In all the others, signifi-
cant reductions in DXA and SPA density were reported.
From this cross-sectional study it can be concluded that
patients with the benign hypermobility syndrome have sig-
nificantly lowered t-scores referring to the volumetric den-
sities measured by pQCT, bone structure, and bone strength
data but never reached the threshold criterium for osteopo-
rosis as proposed by the WHO [29].
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