Bone mineral density is not diminished by mild to moderate

Transcription

1 Kidney Interntionl, Vol. 61 (2002), pp Bone minerl density is not diminished by mild to moderte chronic renl insufficiency CHI-YUAN HSU, STEVEN R. CUMMINGS, CHARLES E. MCCULLOCH, nd GLENN M. CHERTOW Division of Nephrology, Prevention Science Group, nd Division of Biosttistics, University of Cliforni, Sn Frncisco, Sn Frncisco, Cliforni, USA Bone minerl density is not diminished by mild to moderte stge renl disese (ESRD) dilysis ptients hve rechronic renl insufficiency duced bone minerl density (BMD) nd incresed hip Bckground. Persons with end-stge renl disese re t higher risk for osteopeni nd hip frcture reltive to the gereduced BMD s result of bnormlities in cid-bse frcture rtes [2, 3]. Ptients with CRI my lso hve mtched generl popultion. Persons with mild to moderte chronic renl insufficiency (CRI) my hve reduced bone min- nd vitmin D-prthyroid hormone (PTH) homeoerl density (BMD) s result of bnormlities in cid-bse stsis. nd vitmin D-prthyroid hormone homeostsis. Methods. We nlyzed dt on 13,848 dults ged 20 nd Metbolic cidosis, s indicted by decresed serum bove from the Third Ntionl Helth nd Nutrition Exmintion Survey (NHANES III; ). Regression models with even modest reductions in GFR [4]. Chronic met- bicrbonte, hs been detected by some investigtors were used to determine the reltionship between femorl BMD bolic cidosis my led to bone buffering nd slow dissond renl function, the ltter ssessed using serum cretinine, blood ure nitrogen or Cockcroft-Gult cretinine clernce. lution of bone minerl [5]. Short-term orl dministr- To control for confounding, we fit sex-strtified models tht tion of bicrbonte in postmenopusl women improves djusted for ge, weight, height, rce-ethnicity, menopusl clcium nd phosphorus blnce nd reduces bone resttus, estrogen use, ctivity level, fmily history of osteoporo- sorption [6]. sis, diuretic use, nd dietry intke of clcium nd lcohol. Results. Although subjects with reduced renl function hd Mny persons with mild to moderte CRI lso hve significntly lower femorl BMD in undjusted nlysis, the decresed serum 1,25(OH) 2 vitmin D nd incresed ssocition between CRI nd bone minerl density ws extin- PTH levels [7] nd their bone biopsies show evidence guished fter djustment in the multivrite models. In fct, of PTH excess nd incresed bone turnover [8]. Biocontrolling for only sex, ge nd weight ws sufficient to extinchemicl mrkers of bone turnover hve been found to guish ny negtive ssocition between decresed renl funccorrelte with PTH levels nd GFR [9]. A low 1,25(OH) 2 tion nd decresed bone minerl density. Conclusion. Although subjects with worse renl function vitmin D level is n independent risk fctor for hip hve significntly lower femorl BMD, this ssocition cn be frctures [10]. explined by confounding, principlly by sex, ge nd weight. After tking into ccount the fcts tht women, older individu- Severl previous studies hve found tht persons with ls nd smller individuls hve less renl function nd lower CRI hve decresed BMD [9, 11 16]. These studies hve BMD, renl function itself is not independently ssocited with been limited by smll smple sizes, lck of rcil or ethnic BMD. diversity nd, perhps most importntly, filure to djust dequtely for some key confounders such s sex, ge nd weight [9, 11 16]. The generlizbility of these find- There is incresing interest in understnding nd tret- ings to persons with CRI in the generl popultion (tht ing the consequences of chronic renl insufficiency is, those not necessrily seen by nephrologists or endocri- (CRI), defined here s reduced glomerulr filtrtion rte nologists) is lso uncler. It is importnt to test rigorously (GFR) not requiring renl replcement therpy [1]. Endthe hypothesis tht reduced renl function is n independent risk fctor for decresed BMD given tht 6.2 million Key words: NHANES III, glomerulr filtrtion rte, cretinine clernce, chronic kidney disese, osteopeni, osteoporosis. mg/dl [17] nd osteoporosis nd hip frctures re mjor Americns re estimted to hve serum cretinine 1.5 clinicl nd public helth problems. Received for publiction September 26, 2001 nd in revised form December 4, 2001 In this study, we used ntionlly representtive dt Accepted for publiction December 5, 2001 from Third Ntionl Helth nd Nutrition Exmintion 2002 by the Interntionl Society of Nephrology Survey (NHANES III) ( ) to determine the in- 1814

2 Hsu et l: Bone minerl density in CRI 1815 dependent reltionship between renl function nd femorl BMD fter djusting for potentil confounders. METHODS NHANES III popultion Assessment of co-vrites In ddition to sex, ge nd weight, other co-vrites were considered tht hve been shown in lrge epidemiologicl studies to predict femorl BMD [23]. These include: height; rce-ethnicity (pre-defined in NHANES III s non-hispnic white, non-hispnic blck, Mexicn- Americn, or other); level of physicl ctivity (self re- ported s below verge/verge/bove verge); fmily history of osteoporosis (hip frcture or physicin digno- sis of osteoporosis in biologicl mother); current use of diuretics (thizides nd non-thizides); nd dietry intke of clcium nd lcohol. For women, we lso con- sidered menopusl sttus (lst period 1 yer go) nd The design nd opertion of NHANES III hve been described [18]. Briefly, NHANES III provides cross-sectionl, ntionlly representtive dt on the helth nd nutritionl sttus of the civilin, non-institutionlized U.S. popultion. To chieve this, four-stge smpling design ws used: (1) primry smpling units (PSU) comprising mostly of single counties, (2) re segments within PSUs, (3) households within re segments, nd current use of estrogen (pill or ptch). Dt were ob- (4) persons within households. NHANES III oversmpled tined from NHANES III ptient interview nd 24-hour older persons, Mexicn Americns, nd non-hispnic dietry recll [18]. blcks to obtin relible estimtes in these subgroups. Sttisticl nlysis Mesurement of bone minerl density Sttisticl nlysis ws conducted using SAS v8.01 (Cry, NC, USA). NHANES III ws not rndom sm- ple of the U.S. popultion nd not everyone hd the sme probbility of selection. Approprite smple weights were therefore used to obtin weighted regression esti- mtes from the smpled popultion. The smple weights lso djusted for non-coverge nd non-response [24, 25]. The finl results of the nlysis re thus brodly generlizble to the U.S. popultion. In our primry nlysis, the reltionship between cte- gories of S Cr nd BMD ws determined in sex-strtified generl liner models. In men, S Cr ws ctegorized s 0.8, , (reference), , , , , nd 2.3 mg/dl. In women, S Cr ws ctegorized s 0.6, , (reference), , , , , , nd 2.1 mg/dl. We then djusted for ge, weight, height, rce-eth- nicity, ctivity level, fmily history of osteoporosis, diuretic use nd dietry intke of clcium nd lcohol in sex-strtified multivrite models. For women, we lso djusted for menopusl sttus nd estrogen use. We postulted priori tht sex, ge nd weight were the most importnt potentil confounders of ny ssoci- tion between renl function nd BMD. Therefore sexstrtified nlyses were performed in which terms for ge nd weight were entered both s ctegoricl vribles (10-yer nd 10-kg increments) nd s continuous vribles. The former obvited the need to ssume tht BMD vried linerly with ge or weight nd the ltter controlled for ny residul confounding within ech ge or weight ctegory. In NHANES III, 31,311 subjects were exmined in the mobile exmintion center or t home. A trined individul mesured BMD of the proximl femur on men nd non-pregnnt women ged over 20 yers in the mobile exmintion center using dul energy X-ry bsorptiometry (DXA; Hologic QDR 1000, Wlthm, MA, USA). BMD ws mesured in severl res of the proximl femur: femorl neck, trochnter, intertrochn- ter, nd totl region. Excluded were subjects with bilterl hip frctures nd hip pins or rtificil hips. Detils of the BMD mesurement nd DXA quntity control hve been published [18 20]. Assessment of renl function All NHANES III prticipnts over ge 12 were eligible for mesurement of biochemistry profile tht included serum cretinine (S Cr ) nd blood ure nitrogen (BUN). Excluded from venipuncture were exminees reporting hemophili or recent cncer chemotherpy tretment [21]. The mesure of renl function in our primry nlysis ws S Cr. In secondry nlyses, renl function ws ssessed using BUN (djusted for dietry protein) nd Cockcroft-Gult eqution cretinine clernce (C Cr ) [22]. C Cr (ml/min) (Eq. 1) (140 ge) wt (kg) S Cr (mg/dl) 72 ( 0.85 for femles) We chose not to use Cockcroft-Gult C Cr in the primry nlysis becuse interprettion of ny observed ssocition between Cockcroft-Gult C Cr nd BMD my be clouded by the fct tht sex, ge nd weight, which re used to derive the Cockcroft-Gult C Cr, re three of the most importnt independent correltes of BMD. In secondry nlyses, BUN ws used s mesure of renl function nd ctegorized s 5, 6 10, (reference), 16 20, 21 25, 26 30, 31 35, 36 40, nd 41 mg/dl. Since BUN is lso ffected by dily protein in- tke, we djusted for dietry protein in ll nlyses using

3 1816 Hsu et l: Bone minerl density in CRI BUN s the mesure of renl function. When Cockcroft- hve reduced BMD, this ssocition cn be explined Gult C Cr ws used, subjects were divided into eight by confounding by known predictors of BMD, princictegories [26, 27]: 80 (reference), 70 to 80, 60 plly sex, ge nd weight. After djusting for these fcto 70, 50 to 60, 40 to 50, 30 to 40, 20 to tors, no independent ssocition between renl function 30 nd 20 ml/min. nd BMD ws found. To our knowledge, this is the lrgest study testing the hypothesis tht reduced renl RESULTS function is n independent risk fctor for decresed BMD. Since NHANES III is ntionlly representtive NHANES III popultion smple, these results should be brodly generlizble. There were 7132 women nd 6716 men with techni- Previous studies showing tht CRI is ssocited with clly cceptble DXA scns nd mesured S Cr vlues. reduced BMD hd severl limittions, including lck of The chrcteristics of the study popultion re described dequte djustment for key confounders such s sex, in Tble 1. Since this study popultion ws not rndom ge or weight [9, 11, 15]. For exmple, Rix et l found smple of the U.S. popultion, prevlence of CRI shown tht qurtiles of GFR predicted BMD. However, 24 of reflects not only the prevlence of CRI in the U.S. popu- 28 subjects in their best GFR qurtile were men, comltion but lso the effects of smpling s older persons, pred with 20 of 28 subjects in the middle two qurtiles Mexicn-Americns nd non-hispnic blcks were in- nd 18 of 28 subjects in the worse GFR qurtile [9]. tentionlly over-represented. (These groups were subse- Since men hve significntly higher BMD thn women, quently weighted less in the regression nlysis in order determining the independent ssocition between GFR for the finl results to be brodly generlizble.) nd BMD is problemtic. Similrly, in study of 36 women nd 33 men with CRI by Binchi et l, inform- Femorl bone minerl density nd renl function tion on weight ws not presented [15], lthough weight Bone minerl density of femorl neck, trochnter re- strongly predicts both xil nd ppendiculr bone mss gion, intertrochnter region nd totl femorl region [23, 28]. were highly correlted (Person correltion coefficients The importnce of confounding is confirmed in study ). by Buchnn et l of 19 postmenopusl Cucsin In univrite nlysis, both women nd men with women. Although mesured C Cr ws significntly correhigher S Cr hd lower femorl neck BMD (Tble 2). How- lted with lumbr BMD (P 0.03), this reltionship ever, there ws no significnt reltionship between S Cr becme non-significnt (P 0.60) fter ge ws entered nd BMD fter djusting for ge, weight, height, rce- into the model [12]. Similrly, Shermn et l found ethnicity, ctivity level, fmily history of osteoporosis, mong 311 mostly white subjects tht there ws no ssodiuretic use, dietry intke of clcium nd lcohol nd, cition between femorl neck, spine or rdius BMD with in women, menopusl sttus nd estrogen use (Tble mesured C Cr fter djusting for ge [14]. 2). The expected independent ssocition between these Our results suggest tht lthough bnormlities in other fctors nd BMD were ll confirmed in our multicid-bse nd vitmin D-PTH homeostsis could be detvrite models except in the cses of height nd clcium rimentl to bone mss, the mgnitude of these effects nd lcohol intke (where P 0.05). Similr results were my be smll, t lest mong persons with mild or moderobtined when we exmined BMD of the trochnter, te CRI. ESRD ptients my suffer osteoporosis becuse intertrochnter or totl femorl regions (dt not shown). of other risk fctors not prevlent in the CRI popultion, In univrite nlyses, women nd men with higher such s immobiliztion nd gondl dysfunction [2]. BUN nd lower Cockcroft-Gult C Cr vlues lso hd The findings of the present report should be interprelower femorl neck BMD (Tbles 3 nd 4). Agin, howted in the context of the study design. We do not hve ever, in multivrite nlyses, neither BUN nor Cockinformtion on bone histology. Mlluche et l performed croft-gult C Cr ws n independent predictor of BMD bone biopsies on 50 subjects nd found tht osteoclstic (Tbles 3 nd 4). surfce resorption ws bnormlly high when the GFR In fct, in sex-strtified nlyses, djusting for ge nd fell below 50 ml/min/1.73 m 2 nd endostel fibrosis pweight only ws sufficient to extinguish ny negtive pered below GFR of 30 ml/min/1.73 m 2 [8]. Few ssocition between femorl neck BMD nd renl funcother studies exmined bone histology mong CRI subtion (ssessed by S Cr, BUN or Cockcroft-Gult C Cr ). Age nd weight themselves remined powerful independent jects nd little is known bout how bone histology corre- predictors of BMD in ll multivrite nlyses. ltes with BMD in this popultion. Bone minerl density in NHANES III subjects ws mesured only in the proximl femur nd not elsewhere. DISCUSSION This my explin in prt why our results differ from In this study of 13,848 NHANES III exminees, we those of Yendt et l [13, 16], who studied 114 older white found tht lthough subjects with worse renl function women with S Cr 1.3 mg/dl. These uthors found tht

4 Hsu et l: Bone minerl density in CRI 1817 Tble 1. Chrcteristics of the NHANES III study popultion Prmeter Women (N 7132) Men (N 6716) Age yers Weight kg Height cm Rce-ethnicity (non-hispnic white/non-hispnic blck/mexicn-americn/other) % 44/28/25/4 42/26/29/4 Post-menopusl 3411 (48%) Estrogen use 491 (7%) Activity level (below verge/verge/bove verge/ missing or unknown) % 24/46/29/2 17/45/36/2 Fmily history of osteoporosis 508 (7%) 365 (5%) Diuretic use 803 (11%) 496 (7%) Dietry intke of clcium mg/dy Dietry intke of lcohol g/dy Femorl neck bone minerl density (BMD) g/cm BMD of trochnter region g/cm BMD of intertrochnter region g/cm BMD of totl femorl region g/cm Serum cretinine mg/dl Blood ure nitrogen mg/dl Cockcroft-Gult C Cr ml/min Number of subjects with S Cr 0.6 mg/dl 41 (1%) 0.8 mg/dl 83 (1%) mg/dl 1498 (21%) mg/dl 1390 (21%) mg/dl 3843 (54%) mg/dl 3186 (47%) mg/dl 1316 (18%) mg/dl 1427 (21%) mg/dl 252 (4%) mg/dl 373 (6%) mg/dl 107 (2%) mg/dl 132 (2%) mg/dl 35 (0.5%) mg/dl 48 (1%) mg/dl 13 (0.2%) mg/dl 23 (0.3%) 2.1 mg/dl 27 (0.4%) 2.3 mg/dl 54 (1%) BUN 5 mg/dl 66 (1%) 42 (1%) 6 10 mg/dl 2005 (28%) 899 (13%) mg/dl 3154 (44%) 2948 (44%) mg/dl 1324 (19%) 1920 (29%) mg/dl 378 (5%) 632 (9%) mg/dl 124 (2%) 158 (2%) mg/dl 40 (1%) 56 (1%) mg/dl 13 (0.2%) 27 (0.4%) 41 mg/dl 28 (0.4%) 34 (1%) C Cr 80 ml/min 3468 (49%) 4137 (62%) 80 C Cr 70 ml/min 1040 (15%) 809 (12%) 70 C Cr 60 ml/min 861 (12%) 612 (9%) 60 C Cr 50 ml/min 700 (10%) 474 (7%) 50 C Cr 40 ml/min 529 (7%) 365 (5%) 40 C Cr 30 ml/min 365 (5%) 233 (3%) 30 C Cr 20 ml/min 149 (2%) 67 (1%) C Cr 20 ml/min 20 (0.3%) 19 (0.3%) All vlues re unweighted men stndrd devition unless otherwise stted. Reference group S Cr even fter djusting for ge, body surfce re nd 24- group. Since it is mong these individuls tht the most hour urine cretinine, mesured C Cr ws still independently severe cid-bse nd vitmin D-PTH disturbnces occur, ssocited with rdil bone minerl content nd detrimentl renl effects on BMD my develop lte in lumbr BMD. Yendt et l did not mesure femorl BMD the disese process nd further studies focusing on p- [13, 16]. tients with dvnced CRI re therefore needed. Given the smll number of NHANES III prticipnts Renl function ws ssessed using S Cr, BUN nd Cockwith dvnced CRI (such s, close to requiring dilysis), croft-gult C Cr since ctul mesurements of GFR were we hve reltively little ccurcy in studying this sub- not vilble. However, our null result is unlikely due

5 1818 Hsu et l: Bone minerl density in CRI Tble 2. Reltionship between femorl neck bone minerl density (g/cm 2 ) nd ctegories of serum cretinine (S Cr ) Gender Undjusted P vlue Adjusted P vlue Women S Cr 0.6 mg/dl 0.08 [ 0.18, 0.03] [ 0.11, 0.01] mg/dl 0.01 [ 0.02, 0.01] [ 0.02, 0.00] mg/dl reference reference mg/dl 0.02 [ 0.04, 0.01] [ 0.00, 0.01] mg/dl 0.08 [ 0.11, 0.05] [ 0.00, 0.04] mg/dl 0.13 [ 0.17, 0.10] [ 0.04, 0.01] mg/dl 0.14 [ 0.19, 0.08] [ 0.05, 0.05] mg/dl 0.14 [ 0.20, 0.08] [ 0.13, 0.01] mg/dl 0.12 [ ] [ 0.11, 0.04] 0.33 Men S Cr 0.8 mg/dl 0.03 [ 0.08, 0.03] [ 0.09, 0.03] mg/dl 0.00 [ 0.02, 0.01] [ 0.02, 0.01] mg/dl reference reference mg/dl 0.01 [ 0.00, 0.03] [ 0.00, 0.02] mg/dl 0.01 [ 0.04, 0.03] [ 0.01, 0.04] mg/dl 0.05 [ 0.11, 0.01] [ 0.02, 0.04] mg/dl 0.13 [ 0.18, 0.07] [ 0.08, 0.03] mg/dl 0.09 [ 0.22, 0.04] [ 0.07, 0.12] mg/dl 0.10 [ ] [ 0.07, 0.05] 0.76 Adjusted for ge, weight, height, rce-ethnicity, ctivity level, fmily history of osteoporosis, diuretic use, dietry intke of clcium nd lcohol; nd menopusl sttus nd estrogen use in women (vlues in brckets re 95% confidence intervls for prmeter estimtes) Tble 3. Reltionship between femorl neck bone minerl density (g/cm 2 ) nd ctegories of blood ure nitrogen (BUN) Undjusted Gender (except for protein intke) P vlue Adjusted P vlue Women BUN 5 mg/dl 0.06 [0.01, 0.11] [ 0.03, 0.04] mg/dl 0.03 [0.02, 0.04] [ 0.02, 0.00] mg/dl reference reference mg/dl 0.06 [ 0.07, 0.05] [ 0.01, 0.01] mg/dl 0.10 [ 0.12, 0.08] [ 0.02, 0.02] mg/dl 0.15 [ 0.19, 0.12] [ 0.05, 0.01] mg/dl 0.13 [ 0.18, 0.08] [ 0.01, 0.04] mg/dl 0.20 [ 0.26, 0.13] [ 0.07, 0.01] mg/dl 0.11 [ 0.20, 0.02] [ 0.08, 0.04] 0.43 Men BUN 5 mg/dl 0.01 [ 0.06, 0.08] [ 0.02, 0.08] mg/dl 0.00 [ 0.02, 0.01] [ 0.03, 0.00] mg/dl reference reference mg/dl 0.02 [ 0.03, 0.01] [ 0.00, 0.02] mg/dl 0.03 [ 0.05, 0.01] [0.01, 0.04] mg/dl 0.08 [ 0.11, 0.05] [ 0.01, 0.05] mg/dl 0.09 [ 0.16, 0.03] [ 0.03, 0.06] mg/dl 0.06 [ 0.12, 0.00] [0.02, 0.13] mg/dl 0.12 [ 0.17, 0.08] [ 0.03, 0.06] 0.62 Adjusted for ge, weight, height, rce-ethnicity, ctivity level, fmily history of osteoporosis, diuretic use, dietry intke of protein, clcium nd lcohol; nd menopusl sttus nd estrogen use in women (vlues in brckets re 95% confidence intervls for prmeter estimtes) is no independent ssocition between renl function nd BMD. To conclude, in lrge study of ntionlly representtive NHANES III prticipnts, we found no evidence to support the hypothesis tht decresed renl function (with its ttendnt metbolic bnormlities) is n inde- pendent risk fctor for decresed BMD. This is in contrst to other dverse consequences of CRI, such s decresed hemtocrit, which cn be redily detected even mong individuls with mild to moderte CRI to misclssifiction of renl function. We were ble to confirm other investigtors finding tht there ws strong univrite ssocition between BMD nd renl function. Furthermore, using these three prmeters of renl function nd the specific selected ctegories, we were previously ble to demonstrte robust reltionships between renl function nd hemtocrit in both men nd women (lthough only the Cockcroft-Gult C Cr results were reported) [26, 27]. This rgues tht within the confidence intervls presented in Tbles 2 to 4, there truly

6 Hsu et l: Bone minerl density in CRI 1819 Tble 4. Reltionship between femorl neck bone minerl density (g/cm 2 ) nd ctegories of cretinine clernce Gender Undjusted P vlue Adjusted * P vlue Women C Cr 80 ml/min reference reference 80 C Cr 70 ml/min 0.08 [ 0.09, 0.07] [ 0.01, 0.01] C Cr 60 ml/min 0.10 [ 0.12, 0.09] [0.00, 0.03] C Cr 50 ml/min 0.17 [ 0.19, 0.16] [ 0.01, 0.03] C Cr 40 ml/min 0.23 [ 0.24, 0.21] [ 0.01, 0.03] C Cr 30 ml/min 0.28 [ 0.30, 0.27] [ 0.02, 0.03] C Cr 20 ml/min 0.31 [ 0.33, 0.29] [ 0.03, 0.04] 0.73 C Cr 20 ml/min 0.31 [ 0.36, 0.25] [ 0.09, 0.01] 0.12 Men C Cr 80 ml/min reference reference 80 C Cr 70 ml/min 0.09 [ 0.11, 0.08] [ 0.01, 0.02] C Cr 60 ml/min 0.11 [ 0.13, 0.09] [0.00, 0.05] C Cr 50 ml/min 0.16 [ 0.18, 0.14] [ 0.01, 0.04] C Cr 40 ml/min 0.18 [ 0.20, 0.15] [ 0.01, 0.05] C Cr 30 ml/min 0.22 [ 0.24, 0.20] [ 0.03, 0.02] C Cr 20 ml/min 0.23 [ 0.28, 0.17] [ 0.04, 0.07] 0.64 C Cr 20 mllmin 0.06 [ 0.25, 0.13] [ 0.07, 0.24] 0.30 Adjusted for ge, weight, height, rce-ethnicity, ctivity level, fmily history of osteoporosis, diuretic use, dietry intke of clcium nd lcohol; nd menopusl sttus nd estrogen use in women (vlues in brckets re 95% confidence intervls for prmeter estimtes) [26, 27]. Whether the risk of hip frcture in persons with 9. Rix M, Andressen H, Eskildsen P, et l: Bone minerl density nd biochemicl mrkers of bone turnover in ptients with predil- ESRD is relted to n ccelerted loss of BMD with ysis chronic renl filure. Kidney Int 56: , 1999 dvnced CRI or to other unrelted fctors (such s 10. Cummings SR, Browner WS, Buer D, et l: Endogenous hor- propensity to fll) is unknown. Further studies re mones nd the risk of hip nd vertebrl frctures mong older women. N Engl J Med 339: , 1998 needed to define fully the metbolic nd functionl con- 11. Berlyne GM, Ben-Ari J, Kushelevsky A, et l: The etiology of sequences of CRI. senile osteoporosis: Secondry hyperprthyroidism due to renl filure. Qurt J Med 44: , 1975 ACKNOWLEDGMENTS 12. Buchnn JR, Myers CA, Greer RB: Effect of declining renl function on bone density in ging women. Clcif Tissue Int 43:1 6, Drs. Hsu nd Chertow re supported by the Ntionl Institutes of 1988 Helth (RO1 DK nd K23 DK 61520). The uthors thnk Dr. 13. Yendt ER, Cohnim M, Jrzylo S, et l: Bone mss is relted to Anthony Sebstin for his comments on erlier drfts of the mnucretinine clernce in norml elderly women. J Bone Miner Res script. 6: , Shermn SS, Tobin JD, Hollis BW, et l: Biochemicl prmeters Reprint requests to Chi-yun Hsu, M.D., M.Sc., Division of Nephrolssocited with low bone density in helthy men nd women. J ogy, University of Cliforni, Sn Frncisco, Room 672 HSE, 513 Pr- Bone Miner Res 7: , 1992 nssus Avenue, Sn Frncisco, Cliforni , USA. 15. Binchi ML, Colntonio G, Montesno A, et l: Bone mss E-mil: hsuchi@medicine.ucsf.edu sttus in different degrees of chronic renl filure. Bone 13: , Yendt ER, Cohnim M, Jrzylo S, et l: Reduced cretinine REFERENCES clernce in primry osteoporosis in women. J Bone Miner Res 8: , Hsu CY, Chertow GM: Chronic renl confusion: Insufficiency, 17. Jones CA, McQuilln GM, Kusek JW, et l: Serum cretinine filure, dysfunction, or disese. Am J Kidney Dis 36: , 2000 levels in the US popultion: Third Ntionl Helth nd Nutrition 2. Lindberg JS, Moe SM: Osteoporosis in end-stte renl disese. Exmintion Survey. Am J Kidney Dis 32: , 1998 [errtum] Semin Nephrol 19: , Ntionl Center for Helth Sttistics: Third Ntionl Helth 3. Alem AM, Sherrrd DJ, Gillen DL, et l: Incresed risk of hip nd Nutrition Exmintion Survey, , Pln nd Opertion frcture mong ptients with end-stge renl disese. Kidney Int of the Third Ntionl Helth nd Nutrition Exmintion Survey, 58: , (CD-ROM) (revised 9/97). Hyttsville, MD, Center for 4. Frssetto LA, Morris RC Jr, Sebstin A: Effect of ge on blood Disese Control nd Prevention, 1996 cid-bse composition in dult humns: Role of ge-relted renl 19. Looker AC, Johnston CC Jr, Whner HW, et l: Prevlence of functionl decline. Am J Physiol 271:F1114 F1122, 1996 low femorl bone density in older U.S. women from NHANES 5. Lemnn J Jr, Litzow JR, Lennon EJ: The effects of chronic cid III. J Bone Miner Res 10: , 1995 lods in norml mn: Further evidence for the prticiption of 20. Looker AC, Orwoll ES, Johnston CC Jr, et l: Prevlence of bone minerl in the defense ginst chronic metbolic cidosis. J low femorl bone density in older U.S. dults from NHANES III. Clin Invest 45: , 1966 J Bone Miner Res 12: , Sebstin A, Hrris ST, Ottwy JH, et l: Improved minerl 21. Ntionl Center for Helth Sttistics: Third Ntionl Helth blnce nd skeletl metbolism in postmenopusl women treted nd Nutrition Exmintion Survey, , Field Opertions with potssium bicrbonte. N Engl J Med 330: , 1994 Reference Mnuls (CD-ROM) (revised 9/97). Hyttsville, MD, 7. Pitts TO, Pirino BH, Mitro R, et l: Hyperprthyroidism nd Center for Disese Control nd Prevention, ,25-dihydroxyvitmin D deficiency in mild, moderte, nd severe 22. Cockcroft DW, Gult MH: Prediction of cretinine clernce renl filure. J Clin Endocrinol Metb 67: , 1988 from serum cretinine. Nephron 16:31 41, Mlluche HH, Ritz E, Lnge HP, et l: Bone histology in incipi- 23. Orwoll ES, Buer DC, Vogt TM, Fox KM: Axil bone mss in ent nd dvnced renl filure. Kidney Int 9: , 1976 older women. Ann Intern Med 124: , 1996

7 1820 Hsu et l: Bone minerl density in CRI 24. Ntionl Center for Helth Sttistics: Third Ntionl Helth between hemtocrit nd renl function in men nd women. Kidney nd Nutrition Exmintion Survey, , Anlytic nd Reporting Int 59: , 2001 Guidelines (CD-ROM) (revised 9/97). Hyttsville, MD, 27. Hsu CY, McCulloch CE, Curhn GC: Epidemiology of nemi Center for Disese Control nd Prevention, 1996 ssocited with chronic renl insufficiency mong dults in the 25. Ntionl Center for Helth Sttistics: Third Ntionl Helth Unites Sttes: Results from NHANES III. J Am Soc Nephrol nd Nutrition Exmintion Survey, , Weighting nd Estimtion 13: , 2002 Methodology (CD-ROM) (revised 9/97). Hyttsville, MD, 28. Buer DC, Browner WS, Culey JA, et l: Fctors ssocited Center for Disese Control nd Prevention, Hsu CY, Btes DW, Kupermn GJ, Curhn GC: Reltionship with ppendiculr bone mss in older women. Ann Intern Med 118: , 1993