]>MAT1601S0378-5122(01)00241-910.1016/S0378-5122(01)00241-9Elsevier Science Ireland LtdFig. 1Steep mode evaluation of skin tensile strength. Recorded mechanical parameters during variations in the elevation of skin (E, mm) in time (T, s). Ue=elastic (immediate) distension of the skin during the first traction (0.15 s); Uv=visco-elastic deformation until the maximum distension (MD) of the skin is reached at completion of the first traction (5 s); RD=residual deformation of the skin at the end of the first cycle (10 s).Fig. 2Progressive mode evaluation of skin strength. Typical recording of the elevation (E, mm) of skin during a progressive increase (25 mbar/s) in a 20 s suction-on (S, mbar) until the maximum distension (MD) of the skin obtained under the 500 mbar suction, followed by a 20 s suction-off decrease at the same rate. Hysteresis (HY) is defined by the area delimited by the suction–relaxation curves.Table 1Demographic dataMenopausal womenNumberAgeMenopause ageDuration of HRTUntreated6059.3±6.850.6±2.90HRT6057.9±7.149.9±2.37.7±4.6Time is expressed in years (mean±S.D.).Table 2Values of BMD and tensile strength of the skin in the untreated menopausal groupMethod/parameterMean±S.D.CV (%)MedianRangeBone mass densityHip0.799±0.136170.7850.546–1.113Lumbar spine0.872±0.144170.8480.598–1.233Femoral neck0.681±0.113170.6620.504–0.964Skin, steep modeMD (μm)357.5±131.637385100–500BE (%)67.4±15.82364.014–100VER (%)63.2±59.69436.76–240Skin, progressive modeMD (μm)363.0±127.335395100–610BE (%)40.5±17.94433.70–81.8HY (AU)2023±549.72720221075–3292Abbreviations: MD, maximum distension; BE, biologic elasticity; VER, visco-elastic ratio; HY, hysteresis; AU, arbitrary units.Table 3Values of BMD and tensile strength of the skin in the HRT-treated menopausal groupMethod/parameterMean±S.D.CV (%)MedianRangeBone mass densityHip0.838±0.136160.8520.412–1.136Lumbar spine0.932±0.161170.9480.620–1.365Femoral neck0.734±0.117160.7040.567–0.959Skin, steep modeMD (μm)272.4±153.25620570–630BE (%)77.8±14.51981.745.9–100VER (%)105.0±68.465110.113.9–270Skin, progressive modeMD (μm)277.6±147.953220100–630BE (%)52.9±18.43551.920.0–86.2HY (AU)1560±600.2381378989–3714Abbreviations: MD, maximum distension; BE, biologic elasticity; VER, visco-elastic ratio; HY, hysteresis; AU, arbitrary units.Table 4Mann–Whitney U-test assessing the difference between the untreated and HRT-treated menopausal groupsMethod/parameterPBone mass densityHipNSLumbar spineNSFemoral neckNSSkin, steep modeMD0.0037BE0.0011VER0.0032Skin, progressive modeMD0.0018BE0.0013HY<0.0001Abbreviations: MD, maximum distension; BE, biologic elasticity; VER, visco-elastic ratio; HY, hysteresis; NS, not significant.Table 5Untreated menopausal group. Coefficient of correlation (r) assessing linear correlations between BMD values and parameters of skin tensile strengthSkin tensile strengthBMD valuesHipFemoral neckLumbar spineSteep modeMD−0.0430.140−0.084BE0.429**0.351*0.200VER−0.276−0.395*0.057Progressive modeMD0.0810.343*−0.0003BE0.2020.2500.183HY0.0400.1410.036(*P<0.05, **P<0.01). Abbreviations: MD, maximum distension; BE, biologic elasticity; VER, visco-elastic ratio; HY, hysteresis.Table 6HRT menopausal group. Coefficient of correlation (r) assessing linear correlations between BMD values and parameters of skin tensile strengthSkin tensile strengthBMD valuesHipFemoral neckLumbar spineSteep modeMD0.1030.394−0.030BE0.2050.4460.168VER−0.118−0.327−0.151Progressive modeMD0.0310.204−0.040BE0.338*0.620*0.385*HY−0.1060.003−0.123(*P<0.05). Abbreviations: MD, maximum distension; BE, biologic elasticity; VER, visco-elastic ratio; HY, hysteresis.Comparative effect of hormone replacement therapy on bone mass density and skin tensile propertiesG.EPiérard*SVanderplaetsenCPiérard-FranchimontDepartment of Dermatopathology, Belgian SSTC Research Center 5596, University Medical Centre Sart Tilman, B-4000 Liege, Belgium*Corresponding author. +32-4-3662408; fax: +32-4-3662976AbstractObjectives: connective tissues constitutive of skin and bones are affected during the climacteric. Hormone replacement therapy (HRT) can help mitigate their atrophy. The aim of this study was to compare the HRT effect on the skin tensile properties and bone mass density. Methods: a total of 120 postmenopausal women (60 untreated, 60 receiving HRT) were enrolled in the study. Skin tensile properties were assessed on the volar forearm using a computerized suction device. A 500 mbar suction was applied through a 4-mm diameter hollow probe. Two operating modes were applied using a steep and a progressive suction, respectively. BMD was measured on the hip, femoral neck and lumbar spine using dual X-ray absorptiometry. Results: in both groups of women skin elasticity was correlated with BMD. HRT significantly reduced the climacteric-associated decline in skin elasticity. A trend in better preserved BMD was also found in these women without, however, reaching significance. Conclusions: it is concluded that measures of the skin tensile properties can be sensitive enough to disclose HRT efficacy upon connective tissue atrophy. Any decrease in skin elasticity during the climacteric should prompt to perform a BMD assessment.KeywordsHormone replacement therapyBone mass densitySkin tensile property1IntroductionBoth skin and bones are collagen-rich structures particularly affected by the climacteric. Indeed, dermal atrophy and osteoporosis are not unfrequently found in the postmenopausal years. Some studies have addressed these biological aspects and their relationships [1–10]. The positive effect of hormone replacement therapy (HRT) to prevent such changes has been shown repeatedly [11–19].It is acknowledged that a relationship exists between the biomechanical properties of connective tissues and their molecular composition and structural organizations [20,21]. In these respects, non-invasive assessments of bone and skin atrophy are useful in clinical practice [22–26]. The measurement of bone mass density (BMD) and skin tensile characteristics are convenient because they are sensitive and reproducible.The aim of the present study was to compare the effect of HRT on BMD and skin tensile strength in postmenopausal women.2Patients and methodsA total of 120 healthy postmenopausal Causasian women were enrolled in this study (Table 1). They were allocated to two groups, namely 60 untreated women and 60 women receiving oral or transdermal HRT. The medical files documented low estradiol level and high serum FSH in untreated women and before HRT initiation in the others. Presence of osteoporotic crusched vertebrae was the exclusion criterion.A computerized suction device (Cutometer SM 474, C+K Electronic, Cologne, Germany) was used to measure the skin tensile properties. Briefly, the device consists of a hand-held hollow probe fitted to a spring, which ensures that the head is applied to the skin at constant pressure. The main unit consists of a vacuum pump that generates a negative pressure up to 500 mbar. Measurements of the skin deformation inside the suction head are monitored by an optical measuring unit with an accuracy of 0.01 mm [27]. In the present study, the probe had a 4-mm diameter aperture. Measurements were taken from the mid volar aspect of the volar forearm in order to minimize the influence of photoageing on the results. Two modalities of measurements bound to distinct graphic representations were used, namely the steep and the progressive suction modes.The steep suction mode was used with one cycle 500 mbar suction for 5 s followed by a 5-s relaxation period. The skin deformation was plotted as a function of time (Fig. 1). The immediate elastic deformation of the skin (Ue, μm) corresponding to the steep linear part of the curve was computed after 0.15 s of suction. The delayed visco-elastic part of the skin deformation under suction (Uv, μm) corresponded to the mechanical creep between 0.15 and 5 s. The maximum distension of skin (MD, μm) was obtained after 5 s of 500 mbar suction and the residual deformation (RD, μm) at completion of the test cycle. The biologic elasticity (BE, %) was derived following BE=102(MD−RD)/MD. The visco-elastic ratio during the suction phase (VER, %) was calculated after VER=Uv/Ue.The progressive suction mode applied an increasing negative pressure at a linear rate of 25 mbar/s for 20 s, followed by a release of the depression at the same rate (Fig. 2). It was recorded as a stress/strain relationship. MD and BE were measured as in the steep suction mode. In addition, hysteresis (HY) corresponding to the area delimited by the traction and relaxation curves was measured in arbitrary units (AU) using image analysis of the stress/strain graphs (MOP Videoplan Kontron, Eching, Germany).BMD was measured by dual X-ray absorptiometry (DXA) of the trabecular bone of the hip, femoral neck and L1–L4 lumbar spine.Magnitude, spread and symmetry of the data were assessed using the Shapiro–Wilk test. The distribution of the values of each parameter was characterized by the range, mean and standard deviation (S.D.). The Mann–Whitney U-test was used to compare the medians from all parameters between untreated and HRT-recipient menopausal women. The coefficient of variation (CV, %) was calculated following CV=(102×S.D.)/M. The coefficient of correlation (r) was applied to evaluate the relationships between BMD and each biomechanical parameter. A P value lower than 0.05 was considered statistically significant.3ResultsAn overview of the data is presented in Tables 2 and 3. The range in BMD values was quite large at each of the three test sites. The interindividual variability in the skin tensile strength was large as well. Significant differences were yielded between the untreated and the HRT-recipient menopausal women with regard to all the skin tensile strength parameters (Table 4). A decrease in MD and HY, and an increase in BE and VER were present in the HRT group compared with the untreated women. By contrast, no difference was disclosed between the BMD values of the untreated and HRT groups.Significant linear correlations were found in untreated menopausal women between both the hip and femoral neck BMD and some of the skin tensile parameters (Table 5). Indeed, positive relationships were found between these BMD and BE given by the steep suction mode. A negative correlation was yielded between BMD values of femoral neck and VER in the steep mode. Another positive correlation was present between femoral neck BMD and MD given by the progressive suction mode. No correlations were disclosed between on the one hand any of the BMD and on the other hand BE and HY in the progressive mode and MD in the steep mode.Significant positive linear correlations were found in the HRT-recipient menopausal women between each set of BMD evaluations and BE given by the progressive suction mode (Table 6). No significant correlations were found between any of the other skin biomechanical parameters and the BMD values.4DiscussionIn an earlier study, we reported for the first time the relationship between BMD and the skin tensile properties as assessed by a computer-assisted suction method [28]. In that overall evaluation conducted in a rather heterogeneous population at risk of developing osteoporosis, the viscoelastic properties of skin were altered when BMD values were abnormal. Particularly BE decreased in parallel with bone atrophy. At variance with the earlier study, the present was focused on menopausal women receiving or not HRT.It is acknowledged that the overall elastic properties of skin decrease with age [21,27,29]. In addition, age-related bone and skin atrophies are well documented and the negative impact of the climactric upon such an evolution is beyond doubt [1,7,8,10,12,16]. As a counterpart, the beneficial effect of HRT to alleviate the trend in osteoporosis and cutaneous climacteric ageing is generally acknowledged [9,17–19,23,24,26]. In the present study, higher BMD values were found in HRT-treated patients, although the differences with unteated women did not reach significance. This contrasts with other longitudinal studies demonstrating the beneficial effect of HRT in the prevention of the climacteric bone atrophy.Skin slackness developing after menopause is likely related to several factors, including the declines in skin collagen content and dermal thickness [23,24]. Some studies have shown that HRT could limit the extent of skin collagen loss in the initial postmenopausal years [12,17,23]. Another factor influencing skin slackness deals with the elastic fibre alteration with estrogen deprivation. However, the possibility of their repair during HRT is controversial [6,13]. The present data confirm the trend towards a better preserved skin elasticity in women receiving HRT. It is noteworthy that the interindividual variations in BE and VER were higher in the untreated group than in the HRT group. Hence, HRT appears to limit, at least to some extent, the range of variations in BE and VER, thus seemingly limiting one facet of intrinsic ageing. A negative correlation was found between the femoral neck BMD and VER. This relationship was earlier reported [28]. A positive correlation between BMD at all locations and BE in the steep and progressive suction modes was earlier shown [28]. Such a result is confirmed by the present data, except for the spine BMD and BE in the steep mode.In conclusion, earlier observations about the relationship between bone and skin are supported by the present findings. We now point out that the beneficial effect of HRT on skin elasticity may prevail on the effects on bone or at least can be detected earlier using the current non-invasive methods. In addition, there is some evidence that the assessment of the skin tensile properties may predict the effect of HRT on osteoporosis prevention. The present study does not promote measurements of the skin tensile properties as a surrogate of BMD determination. However, it appears that a decrease in skin elasticity may represent a clue inciting BMD assessment. Further studies are needed to assess the value of measuring skin tensile properties in predicting osteoporosis.AcknowledgementsWe thank Professor U. Gaspard from the Gynecology Department for his helpful comments.References[1]M.M.BlackS.ShusterE.BottomsOsteoporosis, skin collagen, and androgensBr. Med. J.41970773774[2]M.BrincatC.F.MonizJ.W.W.StuddA.J.DarbyA.MagosD.CooperSex hormones and skin collagen content in postmenopausal womenBr. Med. J.287198313371338[3]M.BrincatC.F.MonizJ.W.W.StuddA.J.DarbyA.MagosG.EmburyE.VersiLong-term effects of the menopause and sex hormones on skin thicknessBr. J. Obstet. Gynaecol.921985256259[4]M.BrincatC.F.MonizS.KabalanE.VersiT.O'DowdA.L.MagosJ.MontgomeryJ.W.W.StuddDecline in skin collagen content and metacarpal index after the menopause and its prevention with sex hormone replacementBr. J. Obstet. Gynaecol.941987126129[5]L.NilasC.ChristiansenRates of bone loss in normal women: evidence of accelerated trabecular bone loss after the menopauseEur. J. Clin. Invest.181988529534[6]J.L.BologniaI.M.BravermanM.E.RousseauP.M.SarrelSkin changes in menopauseMaturitas111989295304[7]D.ChappardC.AlexandreJ.M.RobertG.RiffatRelationships between bone and skin atrophies during agingActa. Anat.1411991239244[8]C.Castelo-BrancoF.PonsE.GratacosA.FortunyJ.A.VanrellJ.Gonzalez-MerloRelationship between skin collagen and bone changes during ageingMaturitas181994199206[9]G.E.PiérardThe quandary of climacteric skin ageingDermatology1931996273274[10]S.E.WhitmoreM.A.LevineRisk factors for reduced skin thickness and bone density. Possible clues regarding pathophysiology, prevention, and treatmentJ. Am. Acad. Dermatol.381998248255[11]B.EttingerH.K.GenantC.E.CannLong-term estrogen replacement therapy prevents bone loss and fracturesAnn. Intern. Med.1021985319324[12]M.BrincatE.VersiC.F.MonizA.MagosJ.TraffordJ.W.W.StuddSkin collagen changes in postmenopausal women receiving different regimens of estrogen therapyObstet. Gynecol.701987123127[13]R.PunnonenP.VaajalahtiK.TeisalaLocal oestriol treatment improves the structure of elastic fibres in the skin of postmenopausal womenAnn. Chir. Gynaecol.7619873941[14]T.StormG.H.ThamsborgT.SteinickeH.K.GenantO.H.SorensenEffect of intermittent cyclical etidronate therapy on bone mass and fracture rate in women with postmenopausal osteoporosisNew Engl. J. Med.322199012651271[15]C.Castelo-BrancoM.DuranJ.Gonzalez-MerloSkin collagen changes related to age and hormone replacement therapyMaturitas151992113119[16]E.F.HollandJ.W.StuddJ.P.ManseelA.LeatherA.J.BaileyChanges in collagen composition and cross-links in bone and skin of osteoporotic postmenopausal women treated with percutaneous estradiol implantsObstet. Gynecol.831994180183[17]R.MaheuxF.NaudM.RiouxR.GrenierA.LemayJ.GuyM.LangevinA randomized double-blind, placebo-controlled study on the effect of conjugated estrogens on skin thicknessAm. J. Obstet. Gynecol.1701994642649[18]M.GibaldiHormone replacement therapy: estrogen after menopausePharmacotherapy161996366375[19]C.B.HammondMenopause and hormone replacement therapy: an overviewObstet. Gynecol.8719962S15S[20]H.OxlungRelationship between the biomechanical properties, composition and molecular structure of connective tissuesConnect. Tissue Res.1519866572[21]G.E.PiérardEEMCO guidance of the in vivo assessment of tensile functional properties of the skin. Part 1: relevance to the structures and ageing of the skin and subcutaneous tissuesSkin Pharmacol. Appl. Physiol.121999352362[22]S.HagiwaraS.O.YangC.GluerE.BendavidH.K.GenantNon-invasibe bone mineral density measurement in the evaluation of osteoporosisRheum. Dis. Clin. North Am.201994651669[23]G.E.PiérardC.LetaweA.DowlatiC.Piérard-FranchimontEffect of hormone replacement therapy for menopause on the mechanical properties of skinJ. Am. Geriatr. Soc.431995662665[24]A.CallensL.VaillantP.LecomteM.BersonY.GallG.LoretteDoes hormonal aging exists? A study of the influence of different hormone therapy regimens on the skin of postmenopausal women using non-invasive measurement techniquesDermatology1931996289294[25]F.HenryC.Piérard-FranchimontG.CauwenberghG.E.PiérardAge-related changes in facial skin contours and rheologyJ. Am. Geriatr. Soc.451997220222[26]C.Piérard-FranchimontF.CornilJ.DehavayF.Deleixhe-MauhinB.LetotG.E.PiérardClimacteric skin ageing of the face. A prospective longitudinal comparative trial on the effect of oral hormone replacement therapyMaturitas3219998793[27]A.B.CuaK.P.WilhelmH.MaibachElastic properties of human skin: relation to age, sex and anatomical regionArch. Dermatol. Res.2821990283288[28]Piérard GE, Piérard-Franchimont C, Vanderplaetsen S, Franchimont N, Gaspard U, Malaise M. Relationships between bone mass density and tensile properties of skin in women. Eur J Clin Invest, in press.[29]C.EscoffierJ.de RigalA.RochefortR.VasseletJ.L.LévêqueP.G.AgacheAge-related mechanical properties of human skin: an in vivo studyJ. Invest. Dermatol.931989353357