Unequal Decrease in Bone Density of Lumbar Spine and Ultradistal Radius in Colles' and Vertebral Fracture Syndromes

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1 Unequl Decrese in Bone Density of Lumbr Spine nd Ultrdistl Rdius in Colles' nd Vertebrl Frcture Syndromes Richrd Estell, Heinz W. Whner, W. Michel O'Fllon, Peter C. mdio, L. Joseph Melton 111, nd B. Lwrence Riggs Endocrine Reserch Unit, Section ofdignostic Nucler Medicine, Deprtment ofhelth Sciences Reserch, nd Deprtment oforthopedics, Myo Clinic nd Myo Foundtion, Rochester, Minnesot 5595 bstrct We mesured bone minerl density (BMD) t the lumbr spine (LS-BMD) nd ultrdistl rdius (UDR-BMD) in 4 postmenopusl norml women nd in 18 postmenopusl osteoporotic women (55 with vertebrl frcture, 34 with Colles' frcture, nd 19 with both frctures). By receiver operting chrcteristic nlysis, LS-BMD ws better thn UDR-BMD (P <.1) s n indictor of vertebrl frcture; the converse ws true for Colles' frcture (P <.1). lthough UDR-BMD nd LS-BMD were lower in ech of the three frcture groups thn in controls (P <.1), the pttern of bone loss differed (P <.1, nlysis of vrince): with vertebrl frcture, LS- BMD decresed reltively more thn UDR-BMD, with Colles' frcture, UDR-BMD decresed reltively more thn LS- BMD; nd with both frctures, decreses in LS-BMD nd UDR-BMD were similr. We conclude tht both types of frcture re cused by excessive bone loss but the difference in bone loss t the two sites is mjor fctor in determining which will frcture. Introduction Involutionl osteoporosis hs been divided into two types on the bsis ofdifferences in bone density, in the ge- nd sex-specific incidence pttern ofthe ssocited frctures, nd in mechnisms of bone loss (1, ). In type I osteoporosis, there is disproportionte nd ccelerted loss of trbeculr bone, nd frctures chrcteristiclly occur t skeletl sites contining lrge mounts oftrbeculr bone: the vertebre nd distl forerm (Colles' frcture). In type II osteoporosis, there is more grdul thinning of both trbeculr nd corticl bone, leding to frctures of the hip, pelvis, nd proximl humerus nd to multiple wedge frctures ofthe vertebre ("dowger's hump"). Type I osteoporosis minly ffects women within 5 yr of menopuse nd is believed to result from fctors relted to estrogen deficiency. Type II osteoporosis ffects men nd women older thn 75 yr nd is believed to result from fctors relted to ging (1). Bone loss from the vertebre in women with type I osteoporosis nd vertebrl frcture hs been extensively studied (1). Much less is known bout the extent of bone loss from the ddress reprint requests to Dr. Riggs, Endocrine Reserch Unit, Myo Clinic, First Street SW, Rochester, MN Received for publiction 16 Februry 1988 nd in revisedform 6 July J. Clin. Invest. The mericn Society for Clinicl Investigtion, Inc /89/1/168/7 $. Volume 83, Jnury 1989, ultrdistl rdius (UDR),I i.e., the distl 3 cm of the rdius, in women with type I osteoporosis nd Colles' frcture or the reltionship of loss t this site to loss in the vertebre. Most densitometric mesurements hve been mde proximl to the usul site of Colles' frcture, in region contining 5-5% trbeculr bone (3-9). In the present study, we mesured bone minerl density (BMD) of the lumbr spine (LS-BMD) nd UDR (UDR- BMD) in women with type I osteoporosis in order to nswer two questions. The first question ws: is mesuring UDR- BMD s effective s mesuring LS-BMD for detecting bone loss from the vertebre in women with vertebrl frcture? If trbeculr bone loss were uniform throughout the skeleton nd if corticl bone density were unchnged, then similr results would be obtined t mesurement sites with similr proportions of trbeculr bone. If mesurement of UDR- BMD provided good estimte of LS-BMD, this would hve prcticl dvntges. The rdius is considerbly esier to mesure thn the spine nd is not beset with rtifcts such s spinl deformities (bone spurs, vertebrl frcture) nd ortic clcifiction tht my confound the mesurement of LS-BMD in older women. We ddressed this question by performing receiver operting chrcteristic (ROC) nlysis. The second question ws: if ll women with type I osteoporosis undergo phse of ccelerted trbeculr bone loss (1), why do some of them hve Colles' frcture nd others hve vertebrl frcture? We tested the hypothesis tht unequl bone loss predisposes some osteoporotic women to vertebrl frcture nd others to Colles' frcture. The null hypothesis is tht the degree of bone loss is similr t sites of predominntly trbeculr bone, nd tht the type of frcture is determined only by externl events such s trum to one site or the other. Bone loss from the lumbr vertebre cn be mesured by dul-photon bsorptiometry. However, in order to mesure the relevnt site in the UDR, it ws necessry to develop method for mesuring BMD t the distl 3 cm of the rdius. This site is composed of predominntly trbeculr bone (1) nd is where Colles' frcture occurs. The method uses singlephoton bsorptiometry nd computer-ssisted imge processing for ccurte repositioning nd selection of the region of interest. Methods Experimentl subjects Norml women. We studied 4 helthy postmenopusl women (Tble I), ged 5-75 yr, who were 1-31 yr postmenopusl. None hd hd menopuse before the ge of 4 yr, hd ny disese or ws tking 1. bbrevitions used in this pper: LS-BMD, lumbr spine bone minerl density; UDR-BMD, ultrdistl rdius bone minerl density; ROC, receiver operting chrcteristic. 168 Estell et l.

2 ny mediction known to ffect bone density, or hd history of pin or stiffness of the wrist. No subject hd vertebrl frcture evident on nteroposterior or lterl rdiogrphs of the lumbr nd thorcic spine. Frcture groups. The ptients with type I osteoporosis were divided into three groups ccording to the type of frctures they hd. The first group (55 women, ged yr) hd only vertebrl frcture. ll hd three or more mild wedge frctures (nterior vertebrl height 75-85% of posterior height) or one or more severe wedge frctures (nterior height < 75% of posterior height) or both. ll frctures hd occurred fter miniml or no trum. Fctors tht might hve resulted in decresed bone density included history of thyrotoxicosis in one, chronic obstructive irwy disese in one, nd surgiclly induced premture menopuse in seven. None hd hd previous tretment with fluoride, but 8 were being treted with clcium supplements (.5- g ofelementl clcium dily) nd 1 hd previously used or currently were using estrogen. The second group (34 women, ged yr) hd only Colles' frcture. The frctures hd occurred 1-8 mo (men, 11.7 mo) before mesurement; they ffected the dominnt forerm in 17 nd the nondominnt forerm in 17. Fctors tht might hve contributed to decresed bone density included history of thyrotoxicosis in two, chronic obstructive irwy disese in two, nd surgiclly induced premture menopuse in three. None were being treted for bone loss. The third group (19 women, ged yr) hd both Colles' nd vertebrl frctures. The Colles' frcture hd occurred 1-31 yr (men, 15 yr) before mesurement nd ffected the dominnt forerm in 8 nd the nondominnt forerm in 1 1. The criteri for vertebrl frcture were the sme s for the first group. Fctors tht my hve resulted in decresed bone density included history of thyrotoxicosis in one nd surgiclly induced premture menopuse in one. None hd hd previous tretment with fluoride or estrogen, but 1 were being treted with clcium supplements (.5- g of elementl clcium dily). Bone densitometry UDR-BMD ws mesured in the nondominnt forerm (or in the uninjured forerm in the Colles' frcture group) by single-photon bsorptiometry with computer-ssisted imge processing. The forerm ws positioned in the scnning pprtus, nd the wrist ws surrounded by wter bg to ensure constnt thickness over the entire scnning pth. Scnning of the distl 3 cm of the rdius begn t the rdil styloid process (identified by plption) nd moved proximlly in -mm steps (tht is, 15 scn lines). The imge (Fig. 1 ) ws displyed on microcomputer (IBM-PC) to confirm correct positioning of the wrist nd then ws stored on floppy disc for subsequent processing. The rdition source ws 151I (photopek, 7 kev) nd the collimtor ws mm X mm. The imge disply progrm llowed selection of regions of interest nd detection of bone edges. The re of interest ws 1 cm long (Fig. 1 B), nd the distl end of this re ws 4 mm proximl to the medil edge of the distl rticulr surfce of the rdius (which ws lwys the line ofpek bone density). We chose this prticulr site becuse it is the site through which Colles' frcture occurs. We determined tht Colles' Tble L Chrcteristics ofptient Groups Osteoporotic women Vertebrl Colles' Both Vrible Norml women frcture frcture frctures Number ge (yr) 6±8 67±5 65± Postmenopuse (yr) 1±8 19±7 16±7 1±9 Weight (kg) 68±13 63±11 7±13 65±1 Vlues given s men±sd. frcture occurs t men distnce of mm (±4 mm, SD) proximl to the tip of the rdil styloid, bsed on mesurements mde on rdiogrphs of Colles' frcture with miniml displcement. Precision of UDR-BMD, determined by duplicte mesurements on premenopusl helthy subjects, ws 1 7%. The vlue for the dominnt rdius ws 3% higher, on verge, thn tht for the nondominnt rdius s determined by mesurements mde on nother helthy premenopusl women. Thus, in women with Colles' frcture of the nondominnt forerm, the dominnt forerm ws mesured nd 3% correction ws mde. LS-BMD ws determined by dul-photon bsorptiometry of vertebre L- to L-4 with the scnning pprtus previously described ( 11) nd '"Gd s the source (photopeks, 44 nd 1 kev). Frctured vertebre were not mesured. The precision ws.%. ntomic studies ofthe rdius Rdii removed from four cdvers were studied to determine the ccurcy of the mesurement nd the proportion of trbeculr bone t the site of mesurement. To determine BMD of the bone specimens, fter removl of surrounding tissue they were ir-dried, deftted, nd embedded in methyl methcrylte. Three to five pieces -7 mm wide were cut with jeweler's sw (Isomet, Buehler Ltd., Lke Bluff, IL), nd -pm sections from the proximl end of the pieces were ground to 1-pm sections before micrordiogrphy; the proportion of trbeculr bone ws estimted by point counting (Tble II; Fig. ). The remining pieces of bone were prtilly shed (5'C for 4 h); then, trbeculr bone ws seprted from corticl bone by dissection nd shed in muffle furnce t 6'C for 4 h. The mount of ech type of bone ws determined by weighing. The results of the ccurcy nlysis re shown in Fig. 3. The regression line does not intersect the yxis becuse the cdver rdii were scnned with the mrrow ft in situ: this method llows correction for the effect of mrrow ft in vivo. The regression line for deftted bone is shown for comprison (I1). The ccurcy ofthe technique (the stndrd error of the estimte of the regression X 1/men) ws 8%. Sttisticl nlysis The bility ofthe two BMD mesurements to discriminte between the norml subjects nd women with vertebrl frcture or women with Colles' frcture ws evluted by pplying the ROC curve pproch (I13, 14). For ech ofthe two BMD mesurements nd for ech frcture group, ll possible cut-off points were defined nd the proportion of helthy subjects bove (the specificity) nd the proportion of osteoporotic subjects below (the sensitivity) ech point were clculted. This yields n ROC curve tht displys the reltionship between sensitivity nd specificity for ech BMD mesurement s discrimintor between the norml nd frcture groups. The re between two ROC curves contrsts the bility of two BMD mesures to discriminte. The res were estimted nd tested (null hypothesis is tht re equls ) by technique developed by Wiend et l.3 The results of LS-BMD nd UDR-BMD were reported in grms per squre centimeter nd in the form of Z scores. Z scores were used for two resons. First, the BMD result ws djusted for fctors tht differ between individuls, such s ge nd weight. Secondly, this pproch converts the devition from norml of BMD vlues t ech of the two scnning sites into SD units nd thus llows estimtion of the reltive deficit in BMD in ech frcture group. Z scores were clculted by two-step procedure. First, the effects of ge, (ge), (ge)3, body weight, height, nd yers postmenopuse on BMD in the 4 norml women were ssessed by multiple regression nlysis. Both LS-BMD nd UDR-BMD correlted most closely with. Precision = (SD of differences between pired BMD mesurements)/(men BMD) X Wiend, H. S., K. Jmes, B. Jmes, nd M. H. Gil Nonprmetric procedures for compring dignostic tests with pired or unpired dt. Unpublished dt. Unequl Bone Loss t the Site offrcture 169

3 I ""6.P - - %, mp,. I ol :-i. I...% 1 k, k p il k B 1% tt :%I 9 % % percentge of Rdil length Figure 1. () Computer-ssisted imge of distl 3 cm of rdius. Use of horizontl nd verticl cursors llows selection of region of interest. Upper pnel displys BMD profile (-xis is logrithm of ttenution; x- xis is scn distnce) selected by horizontl cursors. (B) Trcing of rdiogrph of forerm bones excised postmortem from 94-yr-old mn to show site of mesurement of UDR-BMD. In previous studies ( 11) BMD ws mesured t the midrdius (5%), one-third site, nd distl site (1%); these proportions relte to distnce long the uln, not long the rdius. ge nd body weight: R =.36 (P <.1) nd.9 (P <.1), respectively. Secondly, the regression equtions were used to predict BMD bsed on n individul's ge nd body weight. The Z score for BMD t either site ws then clculted s Z score = (observed BMD Tble II. Trbeculr Bone Content in Rdiifrom Four Cdvers Cdver Trbeculr bone ge t deth Sex By weighing By point counting yr % 33 M M F 6 * 94 M Men * Smples frctured during preprtion for micrordiogrphy. - predicted BMD)/(sy.X) in which sy., is the stndrd devition of BMD vlues bout the regression line. Thus, by definition, the men Z score in norml subjects would be, nd 95% ofnorml subjects would hve Z scores between - nd +. The Z score clcultions were used to nswer two questions. First, did BMD in the frcture groups differ from BMD in the norml group? Under the null hypothesis tht the frcture groups re the sme s the norml group, the men Z score should not differ significntly from ; this hypothesis ws tested by using one-smple t tests. Secondly, ws there reltively greter loss of LS-BMD in the vertebrl frcture group nd reltively greter loss of UDR-BMD in the Colles' frcture group? This hypothesis ws tested by clculting the men difference between LS-BMD Z score nd UDR-BMD Z score mong ech of the frcture groups. Thus, if there ws reltively greter bone loss t LS thn t UDR, the difference LS-BMD Z score minus UDR-BMD Z score would be negtive; conversely, if there ws reltively greter bone loss t UDR thn LS, the difference LS-BMD Z score minus UDR-BMD Z score would be positive. This derived vlue ws used s bsis for sttisticl comprison of the reltive degree of bone loss t the two scnning sites mong groups. fter testing for overll differences mong the groups by one-wy nlysis of vrince, we compred differences between groups by two-smple t tests. 17 Estell et l.

4 Figure. Micrordiogrph of l-,gm sections from the middle of the region of interest in cdver rdius specimens. (Left) Section from 33-yer-old mn; (right) from 94-yer-old mn. Results Trbeculr bone content of UDR. t the UDR site the men percentge of trbeculr bone ws 71% by volume nd 61% by weight (Tble II). Discrimintion offrcture groups. The ROC curves for LS- BMD nd UDR-BMD in women with vertebrl frcture re shown in Fig. 4. For this nlysis, the curve tht is nerest to the top left corner (this corner corresponds to 1% sensitivity nd 1% specificity) represents the best test. Thus, LS-BMD discrimintes osteoporotic women with vertebrl frcture from ge-mtched norml women better thn UDR-BMD does (P <.1). The res under the curves for LS-BMD nd UDR-BMD were 91% nd 78%, respectively. The ROC curves for LS-BMD nd UDR-BMD for women with Colles' frcture re shown in Fig. 4 B. Here UDR-BMD discrimintes better between women with nd those without Colles' frcture thn does LS-BMD (P <.1). The res under the curves for UDR-BMD nd LS-BMD were 73% nd 61%, respectively. The sensitivity nd specificity of the two mesurements in the E C.) - C Co 1.5 r Regression line (untreted bone) r =.97 d Regression line (deftted bone) /-O vertebrl frcture nd Colles' frcture groups re given numericlly in Tble III. Unequl bone loss t sites offrcture. The LS-BMD nd UDR-BMD vlues re given in Tble IV. The percent decreses of men LS-BMD from norml women were 5%, 7%, nd 5%, respectively, in the groups with vertebrl frcture, Colles' frcture, or both frctures. The respective percent decreses of men UDR-BMD from norml women were 15%, 1%, nd %. ll of these decreses were sttisticlly signifi-._i C c ) Un V re under curve, units Figure 3. Reltionship between estimted BMD (re under curve [see Fig. 1], in rbitrry units) nd sh weight per unit length (g/cm) in four cdver rdius specimens. Regression line intersects wxis bove the origin. Eqution used to clibrte the densitometer ws: sh content =.161 X (bone density) Specificity Figure 4. ROC curves showing sensitivity nd specificity of LS-BMD (thin line) nd UDR-BMD (thick line). () In women with vertebrl frctures. (B) In women with Colles' frctures only. Unequl Bone Loss t the Site offrcture 171

5 Tble III. Sensitivity nd Specificity of UDR-BMD nd LS- BMD s Testsfor Vertebrl Frcture nd Colles' Frcture Sensitivity* Specificityt Mesurement t 9% t 5% t 9% t 5% For vertebrl frcture UDR-BMD LS-BMD For Colles' frcture UDR-BMD LS-BMD * t specificities of 9% nd 5%. * t sensitivities of 9% nd 5%. cnt (Tble IV). In the group with vertebrl frcture there ws reltively greter decrese in LS-BMD, in the group with Colles' frcture there ws reltively greter decrese in UDR-BMD, nd in the group with both frctures there were similr decreses in both LS-BMD nd UDR-BMD. The women with vertebrl frcture hd the most negtive men difference (-.76) between LS-BMD Z score nd UDR- BMD Z score, those with Colles' frcture hd the most positive men difference (.4), nd those with both frctures hd n intermedite men difference (-.). These differences mong the three men vlues were sttisticlly significnt (P <.1, nlysis ofvrince). The women with vertebrl frcture lone nd those with both frctures hd reltively greter decrese t LS-BMD thn t UDR-BMD compred with women with Colles' frcture (P <.1, P <., respectively). In both groups of women with vertebrl frcture, the men decreses in LS-BMD were similr (Tble IV); however, those with both vertebrl nd Colles' frctures hd mrginlly greter reduction in UDR-BMD thn did those with vertebrl frcture lone (P =.6). Individul vlues for these reltive differences re shown in Fig. 5. For the group with vertebrl frcture only, 8% of the points fll below the line of identity, indicting tht bone loss ws reltively greter t LS thn t UDR. For the group with Colles' frcture, 68% of the points fll bove the line of identity, indicting tht bone loss ws reltively greter t UDR thn t LS. For the group with both frctures, 9 points fll bove the line of identity nd 1 points fll below, indicting similr reltive decreses t LS nd UDR. Discussion We encountered two technicl problems in developing reproducible nd ccurte technique for mesurement t the UDR. First, repositioning ws found to be of criticl importnce t this site becuse there were lrge chnges in bone minerl content nd in the proportion of trbeculr bone over short distnce. We overcme this by utilizing computer-ssisted imge processing to identify the re of interest on the intensity-modulted bone minerl imge. Some investigtors hve ttempted to solve this problem by scnning t fixed distnce between the rdius nd uln (for exmple, t 5 mm [15] or 8 mm [16]). However, t these sites the bone is less thn 5% trbeculr nd the proportion of trbeculr bone is very vrible. Others hve performed preliminry "scout scn" by computed tomogrphy (5, 17, 18). The second problem ws tht the high proportion of trbeculr bone (Fig. ) is ssocited with lrge mount of ft in the mrrow spce, nd this produces systemtic error in results of scnning with single-energy photon source. This problem ws pprecited by Krjlinen (19) but hs been ignored by subsequent workers (13, 14). We corrected for it by mesuring UDR-BMD in cdver rdius specimens with mrrow ft in situ nd then deftting the bone nd shing the specimen. This regression of sh content on re under the curve ws then used to estimte UDR-BMD. The presence of ft hs mrked effect on UDR-BMD becuse ttenution of the photon bem is less through ft thn through wter; thus, filure to correct for ft within the mrrow spce results in n underestimte of UDR-BMD. Most previous studies of bone loss from the distl rdius in ptients with Colles' frcture scnned t sites proximl to the frcture site (3, 4, 6-9), where the bone is minly corticl; t those sites bone minerl content ws 5-7% below norml. The one exception ws the study by Hesp et l. (5) in which UDR- BMD ws mesured by combined computed tomogrphy/ single photon bsorptiometry technique. It is notble tht they reported reltively lrge decrese (1%) in UDR-BMD s compred with ge- nd sex-mtched norml subjects. In the present study, we lso found tht the men decrese in UDR- BMD in Colles' frcture ptients ws 1%. Tble IV. Bone Density Vlues in Norml Women nd Women With Frctures Osteoporotic women Vrible Norml women Vertebrl frcture Colles' frcture Both frctures bsolute bone mss LS-BMD (g/cm) 1.4±..78±..97±.3.78±.3 LS-BMD(% below norml) UDR-BMD (g/cm).41±.1.35±.1.36±.1.33±.1 UDR-BMD (% below norml) 15 1 Z-scores LS-BMD (SD units) -1.61±.13* -.6±.18t ±.* UDR-BMD (SD units) -.85±.13* -.97±.13* - 1.4±.* Vlues given s men±se. * For difference from norml women, P <.1. t For difference from norml women, P < Estell et l.

6 ) o C.) L- d r- B -4 K 1- ' t h, UDR-BMD, Z-score 3 Figure 5. LS-BMD nd UDR-BMD expressed s Z-scores, in individul women. Oblique line indictes line of identity. () Women with vertebrl frctures. (B) Women with Colles' frctures. (C) Women with both vertebrl nd Colles' frctures. In our study, BMD ws mesured t sites composed minly of trbeculr bone. Our ntomic studies indicted tht the UDR-BMD mesurement site contined bout 7% trbeculr bone, nd others (1,, 1) obtined similr vlues. Most studies hve found tht vertebre contin bout 7% trbeculr bone (, 3). However, in recent study of cdvers of eight elderly women (ged 6-86 yers), Nottestd et l. (4) found the proportion oftrbeculr bone to be 4% in the body nd 4% in the entire vertebre. This low proportion of trbeculr bone my hve been relted to ge nd to bone loss during the terminl illness. Our findings provide nswers to the two questions tht we posed in the Introduction. In nswer to the first question, UDR-BMD is not n pproprite substitute for LS-BMD in ssessing the extent of bone loss from the vertebre in women with vertebrl frcture. ROC curve nlysis showed tht LS- BMD mesurements were much more sensitive nd specific thn UDR-BMD mesurements for seprting osteoporotic ptients with vertebrl frcture from ge- nd sex-mtched norml controls, despite the similrity in content oftrbeculr bone t the two sites. Conversely, UDR-BMD mesurements were more sensitive nd specific thn LS-BMD mesurements for seprting osteoporotic ptients with Colles' frcture from normls. Thus, in order to predict frcture risk in bone, the BMD oftht bone should be mesured-mesurements mde t other prts of the skeleton hve less predictive vlue. The results of LS-BMD mesurements in women with vertebrl frcture were similr to those in our erlier report ( 11); in tht study, 45% of women with vertebrl frcture hd LS- BMD vlues less thn the 5th percentile of normls, compred with 49% in the present study (Z score < 1.645). In tht study, 7% hd distl rdius BMC vlues less thn the 5th percentile, compred with 5% with UDR-BMD vlues less thn the 5th percentile (Z score < 1.645). The higher proportion oftrbeculr bone t the UDR thn t the distl rdius my llow better seprtion of women with nd without vertebrl frcture. These results do differ from those in two recent reports. Ott et l. (5) mesured LS-BMD nd BMC of the distl rdius in postmenopusl women with nd without vertebrl frcture. Using ROC curve nlysis, they found tht the two mesurement sites gve pproximtely equl sensitivity nd specificity. Thus, for sensitivity of 9% (i.e., the vlue we use s our "frcture threshold"), the specificity of LS-BMD in their study ws 1%, wheres in our study it ws 76%; the specificity of distl rdius BMC in their study ws 35%, wheres for UDR- BMD in our study it ws 5%. Thus, the mjor difference between our findings nd those of Ott et l. (5) is better specificity of LS-BMD in our study. Nils et l. (6) reported BMD results in 8 women with vertebrl frcture. The men LS-BMD Z score ws -.43 (it ws in the present study), nd the men UDR-BMD Z score ws -.51 (-.85 in the present study). The results of Ott et l. (5) nd Nils et l. (6) my differ from our results for two resons. We used stricter criteri for dignosing osteoporosis, requiring the presence oft lest three mild nteriorly wedged vertebre; Nils et l. (6) required only one such frcture nd Ott et l. (5) required only two such frctures. Recently, the Dnish group hve further nlyzed their dt. By dividing their osteoporotic subjects into those with nd without compression frctures, Podenphnt et l. (7) now report reltively greter loss of bone density t the lumbr spine in subjects with compression frctures. The precision ofls-bmd in the present study ws.% ( 11); Nils et l. (6) reported precision of 6.%, nd Ott et l. (5) did not report the precision of their method, but the intrpopultion stndrd devition ws greter thn tht reported by others (8). With respect to the second question, differentil bone loss t the site of frcture my explin, in prt, why some women with type I osteoporosis hve vertebrl frcture nd others hve Colles' frcture. Why is there reltively greter bone loss t the LS in women with vertebrl frcture nd greter bone loss t the UDR in those with Colles' frcture, given tht these sites re both composed minly of trbeculr bone? One expl- Unequl Bone Loss t the Site offrcture 173

7 ntion is tht the differences were present t skeletl mturity ("pek bone mss") nd tht subsequent rtes of bone loss were similr. n lterntive explntion is tht there were differences in the subsequent rtes of bone loss t sites mong individuls. The rtes of bone loss my differ between the LS nd the UDR becuse of the different forces to which these bones re subjected: bone loss from the spine my be decresed by weight-bering exercise nd obesity. lso, the rte of bone turnover in the LS my be greter thn tht in the UDR becuse the vertebre contin both red cellulr mrrow (contining the precursors of osteoclsts nd osteoblsts) nd yellow ftty mrrow wheres the UDR contins only the ltter. The proportion of red to yellow mrrow in the vertebre my differ between individuls nd could ccount for differences in rte of bone loss. Osteoporotic women with only vertebrl frcture hd much lrger men decrese in LS-BMD thn did those with only Colles' frcture. However, the men decrese in UDR- BMD ws only slightly lrger in women with Colles' frcture thn in those with vertebrl frcture. Thus, the women with vertebrl frcture re lso t incresed risk for Colles' frcture but hve not yet sustined the necessr' trum such s flling on the outstretched hnd. n lterntive explntion is tht women with Colles' frcture re more likely to fll thn those with vertebrl frcture. In this regrd, Crilly et l. (7) reported tht women with Colles' frcture hd more posturl instbility thn ge-mtched controls. In summry, lthough ptients with type I osteoporosis lose excessive mounts of bone from both the LS nd the UDR, the mounts of bone lost t these two sites vry mong individuls. The reltive decreses t these two sites my contribute to the development of the different frcture syndromes. Whtever the underlying cuse of the unequl bone loss in type I osteoporosis, it ppers tht site-specific mesurements of BMD re the best wy to study these frcture syndromes nd the best wy to estimte frcture risk prospectively. cknowledgments We thnk Jon M. Muhs for coordinting the ptient studies; Drl J. Jech, Robert L. Crlson, nd Willim L. Dunn for ssisting with bone density mesurements; nd Cheryl K. Collins for prepring the mnuscript. This investigtion ws supported in prt by reserch grnt R-765 from the Ntionl Institutes of Helth. References 1. Riggs, B. L., nd L. J. Melton III Involutionl osteoporosis. N. Engl. J. Med. 314: Riggs, B. L., nd L. J. Melton III Evidence for two distinct syndromes of involutionl osteoporosis. m. J. Med. 75: Nilsson, B. E., nd N. E. Westlin The bone minerl content in the forerm of women with Colles' frcture. ct Orthop. Scnd. 45: Jensen, G. F., C. Christinsen, J. Boesen, V. Hegedus, nd I. Trnsbol Reltionship between bone minerl content nd frequency of postmenopusl frctures. ct Med. Scnd. 13: Hesp, R., L. Klenermn, nd L. Pge Decresed rdil bone mss in Colles' frcture. ct Orthop. Scnd. 55: Hrin, M., nd P. Krjlinen Trbeculr osteopeni in Colles' frcture. ct Orthop. Scnd. 57: Crilly, R. G., L. Delquerriere Richrdson, J. H. Roth,.. Vndervoort, K. C. Hyes, nd R.. Mckenzie Posturl stbility nd Colles' frcture. ge geing. 16: Nordin, B. E. C., R. G. Crilly, nd D.. Smith Osteoporosis. In Metbolic Bone nd Stone Disese. nd edition. B. E. C. Nordin, editor. Churchill Livingstone, Edinburgh Krolner, B., E. Tondevold, B. Toft, B. Berthelsen, nd S. P. Nielsen Bone mss of the xil nd the ppendiculr skeleton in women with Colles' frcture: its reltion to physicl ctivity. Clin. Physiol. (Oxf). : Schlenker, R.., nd W. W. VonSeggen The distribution ofcorticl nd trbeculr bone mss long the lengths ofthe rdius nd uln nd the implictions for in vivo bone mss mesurements. 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