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The Mechanical Properties of Skin in Osteogenesis Imperfecta
Birgitte Hansen, MD;
Gregor B. E. Jemec, MD, DMSc
Arch Dermatol. 2002;138:909-911.
ABSTRACT
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Background Skin mechanics may be affected by several dermatological and systemic
conditions. The skin can act as a marker of generalized disease. Osteogenesis
imperfecta (OI) is a heritable disorder characterized by fragile bones caused
by a generalized disorder of collagen. The dermis has a relative increase
of argyrophil and elastic fibers and a deficiency of adult collagen. The collagen
defect is well described, but functional changes in tissue mechanics have
not been studied in the skin. The functional changes may reflect general changes
and may give insight into the pathogenesis of clinical problems in these patients.
Objective To examine skin mechanics (elasticity, distensibility, and hysteresis)
in patients with OI.
Methods Ten patients with OI (mean ± SD age, 45.9 ± 11.5 years)
and 24 age-matched control subjects (mean ± SD age, 43.3 ± 13.8
years) were studied. The suction cup technique was used (Dermaflex; Cortex
Technology, Hadsund, Denmark).
Results Significant differences between the patients and controls were found
in all measurements (P<.002). Skin elasticity
was decreased in patients vs controls (55.5% [range, 50.9%-60.1%] vs 73.8%
[range, 70.3%-77.2%]). Similarly, distensibility was decreased (2.10 mm [range,
1.85-2.35 mm] vs 2.50 mm [range, 2.37-2.63 mm]), as was hysteresis (0.19 mm
[range, 0.15-0.23 mm] vs 0.28 mm [range, 0.27-0.30 mm]).
Conclusions The skin of patients with OI is more stiff and less elastic than normal
skin. It is speculated that similar differences may be found in other tissues
in patients with OI. The results potentially offer a quantitative standardized
measure of OI, which may further our understanding of the underlying physical
problems of these patients, provide better case definitions, and assist in
predicting the prognosis of patients with OI.
INTRODUCTION
QUANTIFICATION IS of great help in the evidence-based clinical management
of disease. Classification of disease denotes its genetic, anatomical, and
molecular levels, while quantification of disease assists in the clinical
management of its severity, risks, and prognosis. Osteogenesis imperfecta
(OI) is a well described disease involving the major connective tissues of
the body, such as bone, skin, cartilage, and blood vessels. Osteogenesis imperfecta
causes a generalized decrease in bone mass (osteopenia and bone brittleness).1 The disorder is frequently associated with blue sclerae,
dental abnormalities (dentinogenesis imperfecta), progressive hearing loss,
and a positive family history. Most patients with OI have several deletions,
insertions, and point mutations in 1 of 2 structural genes coding for type
I procollagen.2 The same mutation, however,
does not always produce the same disease phenotype in terms of severity of
the condition or its clinical course.3 In families
with OI, some members are clinically severely affected, whereas others with
the identical mutation have only a mild disorder. This study was undertaken
to characterize the mechanical properties of the skin in patients with OI
and to determine whether they can be used as a functional measure of the underlying
abnormality and correlated to disease severity.
MATERIALS AND METHODS
Ten patients with OI (8 with type I [3 men and 5 women] and 2 with type
III4 [1 man and 1 woman]) and 24 control subjects
(14 men and 10 women) were studied. The mean ± SD age of the patients
was 45.9 ± 11.5 years and of the controls, 43.3 ± 13.8 years.
The study was in accordance with the principles of the Declaration of Helsinki.
Written informed consent was obtained from all participants.
Skin mechanics were studied using the suction cup technique (Dermaflex;
Cortex Technology, Hadsund, Denmark).5-6
A 100-mm probe (suction cup) is attached to the skin with an adhesive ring,
and a vacuum is applied in 4 cycles of 6 seconds each. Two variables were
studied: distensibility, reflecting the elevation
(in millimeters) of the skin surface in the suction cup following the first
application of suction, and hysteresis, measuring
the change in maximum elevation following successive suction cycles (the "creep"
phenomenon). Elasticity is the relative retraction
following the first suction.
Healthy controls were recruited from the staff of the Department of
Dermatology, Bispebjerg Hospital, Copenhagen, Denmark. None of the controls
had signs or a history of generalized dermatological or connective tissue
disease. For 3 hours before skin measurement, subjects refrained from moisturizer
use or exposure to water to avoid externally induced changes of skin mechanics.7
Standing height was measured to the nearest 1.0 cm, using a stadiometer.
Standing height has been suggested as an overall measure of disease severity
in OI by Lund et al.8
Comparisons between patients and controls and between patient groups
were done by independent t tests. All tests were
2-tailed, and P<.05 was considered significant.
Regression by the least squares method was used for fitting the height and
skin elasticity measurements. These calculations were performed using commercially
available software (SPSS version 10.0; SPSS Inc, Chicago, Ill). Data are given
as mean ± SD.
RESULTS
No abnormalities of skin elasticity or fragility were apparent in the
clinical examination of the patients' skin. However, there were significant
differences between the patients and controls in all suction cup measurements.
Skin elasticity was 55.5% ± 4.6% in the patients and 73.8% ±
3.5% in the controls (P<.001). The distensibility
was 2.10 ± 0.25 mm in the patients and 2.50 ± 0.13 mm in the
controls (P<.001). Hysteresis was 0.19 ±
0.04 mm in the patients and 0.28 ± 0.01 mm in the controls (P<.001) (Table 1).
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Characteristics of Patients With Osteogenesis Imperfecta
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A linear relationship was found between standing height and skin elasticity
in patients with OI (r2 = 0.37; P = .06): percentage of skin elasticity = (30.90 + 0.17)
x height in centimeters.
The patients were divided into groups according to OI type. Consequently,
8 had type I and 2 had type III. Patients with type III had a lower skin elasticity
than those with type I (47.00 ± 7.70 mm vs 57.60 ± 4.50 mm).
However, patients with type I had a much lower skin distensibility (1.98 ±
0.21 mm vs 2.60 ± 0.45 mm). Hysteresis was greater in patients with
type III (0.25 ± 0.05 mm vs 0.18 ± 0.05 mm).
COMMENT
The mechanical properties of the skin in patients with OI are abnormal.
In the present study, all 10 patients with OI had decreased elasticity, distensibility,
and hysteresis compared with controls. These changes differ from age-related
changes, which have been described as increased distensibility and viscosity
(similar to hysteresis).9 Collagen is the only
fibrous protein that has high tensile strength and tensile properties.10-11 Therefore, altered elastic properties
may be interpreted as a reflection of abnormalities in dermal collagen and,
possibly, as an indication of general changes in body collagen. The findings
of this study suggest that the skin is stiffer and less elastic in patients
with OI, which may reflect the connective tissue abnormalities that underlie
the general clinical presentation of the disease, such as bone brittleness.
The correlation between elasticity and distensibility appeared to be altered
between type I (mild to moderate disease, minimal bone deformity, and autosomal
dominant inheritance) and type III (severe disease, progressive bone deformity,
and autosomal recessive inheritance), suggesting additional means of distinguishing
different types of OI, based on mechanical abnormalities of the skin (Figure 1). The current sample size, however,
does not allow for meaningful analysis of subgroups.
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Skin distensibility and elasticity associated with patients' osteogenesis
imperfecta (OI) type vs those of controls.
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Osteogenesis imperfecta can be a severely debilitating disease, and
a method is needed to predict the prognosis in individual patients. The disease
is classified into 4 types, but in clinical practice it may be difficult to
distinguish between them. This is especially the case in childhood, when the
need for a predictive prognosis is the greatest. The problem is compounded
by the fact that, even if the genetic type is known, it is often not possible
to predict the clinical outcome.3 Current classification
does not provide the necessary data for prediction of future impairment. Lund
and coworkers8 have found that a relative reduction
in standing height appears to correlate with OI type and the type of collagen
defect. However, this may be viewed as an explanatory rather than a predictive
association.8 When changes in the skin elasticity
were compared with adult height, a near-significant correlation was found,
supporting this association.
Other connective tissue diseases, such as Marfan syndrome or progressive
systemic scleroderma, are known to involve skin and other organs. In these
cases, changes in the mechanical properties of the skin are paralleled by
similar changes in internal organs (eg, slack skin and aneurysms in Marfan
syndrome, fibrosis of the skin and lungs in progressive systemic scleroderma).
This makes it possible for a dermatological examination of a patient to contribute
to the diagnosis. It is hypothesized that a more quantitative approach may
be of further use in establishing the magnitude of the impairment and in offering
prognostic information to the patient.12
In the present study, abnormal changes in the mechanical properties
of the skin of patients with OI reflected the functional changes of connective
tissue. Although difficult to interpret because of the small number of patients
studied, differences were found between subtypes of OI, suggesting that additional
information may be gathered by biophysical studies. These findings suggest
that in vivo measurement of the mechanical properties of skin may be a relevant,
prognostic factor in the clinical assessment of OI.
AUTHOR INFORMATION
Accepted for publication July 30, 2001.
The participants are acknowledged for their participation; Ulla Pedersen
for skillful technical assistance; and Gerda and Aage Haensch's Foundation,
Copenhagen, Denmark, for their help.
Corresponding author: Birgitte Hansen, MD, Osteoporosis Research
Clinic, Hvidovre University Hospital, University of Copenhagen, Kettegaard
Allé 30, DK–2650 Hvidovre, Denmark (e-mail: bh{at}dadlnet.dk).
From the Osteoporosis Research Clinic, Hvidovre University Hospital,
University of Copenhagen, Copenhagen (Dr Hansen), and Division of Dermatology,
Department of Medicine, Roskilde Hospital, Roskilde (Dr Jemec), Denmark.
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