- Email: [email protected]
Lower mobility and markers of bone resorption in the elderly
Boncw~dMincrol. El=* BAM
49
9(1990)49-57
133258
Lower mobility and markers of bone resorption in the elderly
Paul Lips, Floris C. van Ginkel, J. Coen Nztelenbos, Anje Wiersinga and Wim J.F. van der Vijgh
tmmobd~zation may lead 10 severe bone fox
Physical activily decreavr
might influence bone 10s~.We have evaluated the degree of mobility and
piti
age and lower mobility
parameters of bon turnover in
70 residents of a nursing home (mean age + SD St Y?9 years) and 68 residents of an afd peop+e’s fmme (mean age f SD 84 t 6 years). The mobility was asxsred with a standing and walking scow from 1 (severely disabled) to 5 (standingiwalking without help). When the subjects were anangd
acmding
to in-
neasing walking scrxe from I to 5. iarling urinary bydroxyprolinelcrealinine ratb gradually &creased IramX * 1910142 5~mollmmol (P
D concentrations with increasingwalking xore. Thezz dataindiutethat
lower mobility in the elderly leads to higher bone resorption. which may rupprrsdths forrnatmn of 1.2% dihydrwyvitamin
D.
Immobilization leads to increased bone resorption and bone loss. which may amount to as much as 1% per week 01 more than 30% in 6 months Il.:]; howwer atble!zs kave a higher bone mass ]3] and thus physical activity may prevent age-~.lated bone loss 14.51. Physical activity decreases with age and variation in mobility in the elderly might influence hone loss. Therefore, we have evaluated the degree of mobility and biochemical parameters of bone remodelling in elderly residents of twoinstitutions.
Carrespondence to. Dr P. UPS. Depl of EndocrinaloSy, P.O. Box 7057. X07 MB Amsterdam. The Netherlands.
Academisch Zekenhuis
0169.MM919ivSO3.5D Q IWO Elsevier Snence Publishers B V. (Biomedical Division)
“rije
“nwersitc,,.
50 Subjects and Methods This report is part of a greater study dealing with the effects of vitamin mentation
on vitamin
D status and parathyroid
were 70 residents of a nursing home. ‘Regina
or from their legal representatives. committee
of the university
10 men, mean age
‘De Kimme’ (56 wo-
+ SD 81 f 9 years) and 68 residents of an old people’s home, men, 12 men; 84 * 6 years). Informed
D supple-
function in the elderly 161. Subjects Pacis’ (60 women,
consent was obtained
from the participants
The study protocol was approved by the ethical
hospital. The residents of the old people’s home were
reasonably healthy and more or less active, but the nursing home residents suffered from cardiovascular. less mobile,
neurologfcal,
although
locomotor
not bedridden.
score, which has been used in Dutch score. standing and walking disabled) Table
and other chronic diseases and were
Physical ability institutions
was assessed with a mobility
for several years [7]. With
this
are graded according to a 5-point scale from 1 (severely
to S (able to stand/walk
easily without
1. The scores were obtained
help).
The score is presented
in
in a blind fashion shortly before or after the bio-
chemical studies. Urine
and blood samples were obtained in the nursing home in July and in the old
The subjects were fasted overnight. The first urine in
people’s home in September.
the morning was discarded. The subjects drank several glasses of water and the second urine, collected about 2 h later, was used for detemtination nine ratio (C&r). creatinine
renal phosphate threshold
ratio (Hp/Cr)
(TmP/GFR)
of calciumlcreati-
and hydroxyproline/
[8]. Fasting blood samples were obtained
the same morn-
ing and the plasma or serum were kept frozen until analysis. Serum and/or urine calcium, phosphate, bumin concentrations
were measured
calcium was corrected
for serum albumin
rected calcium
= calcium
was measured
by calorimetry
subject coefficient
HPLC (CPB)
lo-NO, were
(CV)
rum 1,25(OH),D
were 5 and 6%. concentrations
receptor as binding protein.
measured
(PTH(l-84))
volving aminoterminal
cor-
T [8]. The withinratio in a 2-h fast-
purification
by competitive
days) is 7.3%.
Se-
by a Sep-
was by a gradient mixture.
protein
Serum
binding
assay
The intra- and interassay coefficients
respectively.
The detection
of
limit was 3 nmoUI. Se-
were measured by CPB using chicken duodenal
The intra- and interassay CVs were 6 and 15%. respec-
tively. The detection limit is 10 pm&l
man PTH
with chloramine
Further
Serum
Hydroxyproline
column and a hexane-isopropanol
[9,10]. Vitamin
measured by single radial immunodiision index) was calculated
X 0.02 mmol/l.
D metabolites were chromatographed
using rat serum as binding protein.
variation
methods.
using the formula:
subjects on 4 non-consecutive
and eluted with ethanol.
concentrations
phosphatase and al-
laboratory
of the hydroxyproline/cmatinine
in 5 elderly
with a Nucleosil
25(OH)D
(g/l))
after oxidation
rum samples for analysis of vitamin Pak C I8 cartridge
alkaline
concentration
+ (40 - albumin
of variation
ing urine (measured
creatinine.
using standard
[ll].
D
binding protein (DBP) was
The free l,ZS(OH),D
as IOr x molar ratio 1,25(OH),D/DBP
[ll].
index (F-125 Serum intact hu-
was measured by a two-step immunochemical immunoextraction
followed
noassay. The intra-assay and interassay CVswere
method,
by a sensitive midregion 8.3 and 10.2%.
in-
immu-
respectively.
The
51 detection limit was 0.8 pm&l [12]. Serum osteocaltin concentrations were measured at the laboratory of Dr P. Dehnas (Lyon, France) by radiiimmunoassay using a rabbit antiserum against bovine osteocalcin and using kits obtained from ORIS Industrie, Gif SW Yvette, France. Statistical evaluation of the re~tts was made using the SPSSx program [13,14]. The data of the two institutions we-z combined and c-rahtated using analysis of variance (MANCVA) followed by orthogonal polynomial contrast analysis. According to this method, the biochemical data dassified into five groups on the grounds of mobility score were consecutively fitted to a linear or various exponential models, and the significance tested 1141.When the linear model is significant, the data in the five groups show a linear increase cm decrease with increasing mobility score. Biochemical determinants of the standing and walking scores were evaluated by stepwise multiple regression analysis.
Standing and walking scores in the nursing home and old people’s home residents are shown in Table 1. The biochemical parameters varied with ianeasing mobility scores, the results being similar for standing and walking scores. The biochemical results are arranged according to increasing walking score in Tables 2 and 3. T6e mean fasting urinary Ca/Cr and Hp/Cr showed a significant linear decrease within-
Table 1 Mobility score in 70 nursing home residents and 68 old people’s home residents Nursing home
old pwpi&
0 2. Able to stand up and remain standing with personal support 3. Able to stand up with personal support and remain standing with mechanical aid
0
4. Able to stand up and remain standing with difficulty and with/without aid
21
5. Can stand up and remain standing easily without help
1.
Cannot walk either with mechanical or with personal help
2. Able to walk between two
perronror with
one
person and B mechanical aid 3. Can walk with mechanical aid and rupervision (unsafe walkingpattern.
pcor balance)
4. Can walk a limited distance without supervision with/without mechanical aid (stain with help)
9. AL
:o nalk independently for a ;.T,‘~T distance an any surface in&dine: stirs
46
boms
Table 2 Results of 2 h fasting urine in nursing home and old people’s home residents grouped according to walking score Walking scare
n
C&r (mmollmmol)
HplCr (!.tmollmmol)
TmPiGf’R (mmolllj
1 2 3 4 5
15 17 33 3R 32
0.47 + a.43 0.54 * 0.42 0.44 * 0.35 0.33 f 0.23 0.29 t 0.22 P < 0.0.Y
31 f 19 29 * 22 24 * 12 18f 10 14 f 5 P 4 O.ixol’
0.89f0.20 0.74 f 0.14 0.84+0.17 0.83 f 0.19 0.88 ?: 0.15 NS
P < O.Olb
P < 0.001~
---
-
’ Overall significancebetween groups (MANOVA).
b Significanceof linearmodel (contrastanalysis);the expawttial models were not significant.
Table 3 Biochemical parameters of nursing home and old people’s home residents grouped according to walking score Walking score
n
1 2 3 4 5
17 17 33 39 32
1
2 3 4 5
17 17 33 39 32
Crcatinine
Albumin
(runON)
(pn)
Calcium’ (mm&l)
Pbasphate (mm&l)
35.4 * 4.0 38.2k3.1 39.4 t 3.6 40.2 * 3.2 42.6 f 2.5 P< O.wol~
2.41 f 0.12 2.34 f 0.09 2.27 f 0.09 2.36 * 0.08 2.26 * 0.08 P
1.12 f 1.02 * 1.03 f 1.05 * 1.04 f NS
P
PCO.mllb
52 * 28 %?21 93 * 23 89f 18 9of 19 NS
88*19 87+21 92231 92 + 62 81 f 22 NS
3.4 * 3.8 * 3.3 * 35 * 3.4 f NS
1.9 2.7 2.1 1.8 1.6
10 11 19 32 27
6.6 * 5.7 i 7.7 t 6.2f 6.1 *
0.14 0.15 0.15 0.13 0.13
1.5 I.5 2.4 1.8 1.5
P
Walking score
n
zs(G:i)u (nmolil)
135(OH)zD (PnlOku
1 2 3 4 5
17 17 33 39 32
22.2 * 22.6 + 24.6 + 22.5 + 25 5 + NS
56237 65 * 29 79+34 78 * 24 95 * 26 P < o.cw
P < 0.02*
0.8Bf 0.58 1.03 f 0.46 1.24 f 0.47 1.19f0.36 1.39fO3-i P < O.W5’
P<0.001b
P < O.Olb
P< 0.001~
7.7 7.2 12.1 12.5 12.1
’ Overall significancebetween groups (MANOVA) b Significanceot linearnodei (contrastanalysis). ’ Conccted 6x swum albumin.
DBP (mwl) 330 f 327 * 329 * 342 f 355 *
F-1.25 index (molar ratiox loI) 38 20 3n 46 31
53
creasing walking score. Individual values for these parameters are shown in Figs. 1 and 2. The mean values for urinary Hp/Cr were. increased with walking scores 1-3, and in the normal range with walking scores 4 and 5. Serum albumin showed a linear increase with increasing walking scores. The serum calcium mocentration, carrected for semm albumin, decreased significantly in a !&ear way with increasing walking score. Individual values of serum calcium arc shown in Fig. 3. The serum conanr~atiorls of creatinine, phosphate, alkaline phosphatase, FTH(l-fN) and 25(OH)D did not change significantly with increasing walking score. The serum osteocalcin concentration showed a significant change with increasing walking score, but the relationship was non-linear with the highest value at walking score 3. The sexurn concentrations of 1,25(OH),D and DBP and the F-1,25 index showed a significant linear increase with increasing walking snore. Individual values of serum 1,25(OH)JI are shown in Fig. 4. There was a significant negative correlation between strum calcium and serum 1,25(OH)@ (r = -O.z?Jl,P -=z0.001). The mobility scores were lower in the nursing home than in the old people’s home. The mean fasting urinary Hp/Cr ratio was higher (Pc 0X01), and the scram albumin and 1,25(OH),D concentrations were lower (P c 0.001 and P < 0.02, respcctively) in the nursing home residents than in the residents of the old people’s home [6]. The other biochemical parameters were similar in the two instituticms. Because of these differences, the two institutions were also considered separately.
54 The mean fasting HplCr ratio decreased from 31 & 19 to 21 f 12~moUmmol with increasing walking score (l-4) in the nursing home residents (P = 0.17, NS), and from 21 + 11 to 14 + 5 ~moUmmo1 with increasing walking score (3-5) in the old people’s home (P < 0.05). The serum albumin concentration increased from 35.4 & 4.0 to 40.1 2 3.5 g/l with increasing walking score in the nursing home (P c O.OOS) and from 40.2 + 3.0 to 42.6 f 2.5 gA with increasing walking score in the old people’s home (Pc 0.01). The serum l,ZS(OH),D concentration increased with increasing walking score in both institutions, but the increase was not significant. Serum 1,25(OH)zD increased with increasing standing score in the old people’s home from 77 ? 27 to 93 + 26 pmolfl (P c 0.05). Biochemical determinants of the walking score were assessed with stepwise multiple regression analysis. The most important single determinant was serum albumin (multiple R' = 0.28, P < 0.001). When including urinary Ca/Cr (P c 0.001) and serum 1,2S(OH),D (P 5 0.02) in the regression analysis, the multiple RZ increased to 0.44. When the residence of the subjects was taken into account, this was included in the first step (P< O.OOl), the following steps being albumin (P < 0.001) and urinary CalCr (P < 0.02) leading to a multiple R* = 0.55. When assessing the determinants of the standing score, the following parameters were included in the
t
.
Hp/Cr
ratio in residents of a nursing home and old people’s home grouped according lo walking xore. The dotted line indicates the upper refer-
Fis. 2. Individualvaluer of fastingurinaryhydroxyprolinekrcatininc ence limit.
55
calcium .
2.60t -
.
.
:
I -!-
2.40. -
; i _1 f, -i li f
.
--
-T-
: 220 :
f.
c
.
FQ. 3. Individual values of serum calcium (corrected for serum albumin) in resklen~ of a musing imme and old people’s home grouped according to walking score.
1,25(OH),D
1
1
*
3
4 w.king
5 -
Fig. 4. Individual values of serum 1,ZSdihydmx)ritamin D in residents of a ntig home acd old people’s home grouped according to walking so%. ‘l%e doned line indicates the lower reference limb in healthy adults
56 regression analysis in this order: residence (P < O.OOl), urinary HplCr (P c 0.02) and albumin (P < 0.05) leading to a multiple R’ = 0.69.
Discussion Complete immobilization, such as after spinal cord injury, leads to severe bone loss [I]. The effects of partial immobility or lower physical activity are less well known. Physical activity decreases with age and the degree of mobility varies with the residence. Elderly at home or in an old people’s home are usually more mobile and active than geriatric patients in a hospital or a nursing home. The subjects in thii study were more or less healthy inhabitants of an old people’s home and residents of a nursing home, comprising all mobility degrees as is visible from the walking scores. Lower mobility, i.e., low walking score, was associated with higher valuesof serum calcium concentration and fasting urinary calcium and hydroxyprotine excretion, reflecting increased bone resorption. The relatively higher serum calcium conccntration apparently suppressed the formation of 1,25(OH),D, as has been reported during immobilization [15]. This suggests that, in addition to decreased renal function, lower mobility could contribute to the low serum 1,25(OH)P concentration and lower calcium absorption in the elderly [16]. The lower serum 1,25(OHhD in the relatively immobile elderly (walking score l-3) cannot be explained by impairment of renal function, as the serum creatinine concentration was similar in all mobility groups. We would also have expected a lower serum PTH(l-84) in the immobile elderly than in the more active groups, but a relative decrease may have been masked by stimulation of the parathyroid glands by vitamin D deficiency or decreased renal fmtction 14. Since the nursing home residents had lower walking scores and more chronic diseases than the residents of the old people’s home, the increased bone resorption could be attributed to chronic diseases. However, the fasting urinary Ca/Cr ratio was not significantly different between the two institutions [6], but varied significantly with the walking score (Table 2). When considering the two institutions separately, significant changes of the biochemical parameters with the mobility score were also found. Of course, the residence, the degree of mobility and general state of health are closely interrelated, which is reflected by the fact that residence, serum albumin and urinary CalCr ratio are the best prediitars of the walking score according to stepwise multiple regression analysis. Our data suggest that relative immobility is an important factor in bone resorp tion and bone loss in the elderly. However, a definite conclusion cannot be drawn from this cross-sectional study. A further prospective dudy should be performed to determine whether improving the walking score leads to a decrease of bone resorp tion parameters and an increase of the serum 1,25(OH),D concentration.
Acknowledgements We are indebted to participants and personnel of ‘Regina Pacis’ and ‘De Kimme’,
57
to Drs M. Hermans, C. Leering and A. van der Hogen, to MR E. Lommerse and Mr G. Hobson for their help in the study, to the labozzary of Clinical Chemistry, to Mr S. Kuipet for vitamin D metabolic measurements. ro Dr R. Bouillon (University of Leuven) for the estimation of DBP and to Dr P. Delmas (Lyon, France) for the estimation of osteocalcin. This study was supported by the Praeventiefonds. The Hague.
References 1 Minaire I’. Meunier P. Edward C. &mard J, Courvmn P, Bourrct 1. Quardita(ivehiuolodal dam an diwursc&poroGs. C&if TissueRes lP74:17:57~73). 2 Krabmr B. Taft B. Vertebral bone lors: an unheededside cffec! of therapeuticbed rest. Cfin Sci lPS?.@537-540. 3 NilssonBE, Westlin NE. Bonedensityin athletes.Clin Onhop 1971;77:37P-182. 4 Aloia JF, Cohn SH. Ostuni IA. Cane R. Ellis K. Preventionof involutionalbone lossby exacise. Ann Intern Med 1978;89:356-3%. 5 Krplner 9, Taft B, Nielsen SP. Tondevold E. Pbysieal aexist as propbytasjs against imdutinsl venebrsl bone lo%: a controlled trial. clin Sci 1983.64~541-546. 6 Lips P, Wierringa A, Van Ginkcl FC, Jongcn MJM, Nctelenbor JC, Haekeng WHL. Defma PD. Van der Vijgh WJF. The effect of vitamin D supplementarionon vitamin D staus and para~hymid functionin elderly sub@% I Clin Endtinol Metab 1988,67%U-650. 7 Leering C. Validiteit en invaliditeit. In: Schouten1, Leering C, Balder I. cds.,tinbock Gmiati. Utrecht: Bohn, SchekemaandHolkema, 1985:71-79. 8 Bergman 1. Loxfey R. The determination of bydroxyprolioe in urine hydndysarca. Cfin Cbim Acta 1970;27:34?-349. 9 Jongco MJM, Van der Vi&b WJF, Wdlems I-f& Nerclenbos JC. Lips P. Simultaneour, determins tion of 2%hydronyvitamin D, 24,2Sdihydroryvitamin D and 1,25_dihydroxy%tamin Din pizwma or serum. ClinChem 1981:2731757-176Q. 10 Jongen MJM, Kuiper S. Van der Vi&h WIF. Lips P. Netelenbor JC. Imprweloems in the rimulranecms determinationof calcidiol andczdcitriolin humanserumor plasma.1 CUn Chcm “io Biahm 1PSS;26:25-28. 11 Bouillon R, Van Baelen H, De Moor The measummentafthctitamin DbindingprateiDin human serum. J Clm Endacrinal Memb 1977$5:2%5-231. 12 Hacksne WHL, Lips P, Netclcnbor JC, Lips CJM. CliniFd implicabonr of Estim-Jlion of intactparathyroid hormone &T-f) versus total immu&eaclive PM in normal subjecls and hyptqmmtbyroid patients. J Clin Endocrinol Metab 1986,63:447-453. 13 Nie NH. SPSSx u~sr’s guide. New York McGraw-Hill Bmk Co., 14 Nonub M.J. SPSSx Advanced swisrin guide. Nzw York McGraw-Hill Book Co., AF, Adler M, Byen CM, Segre GV, Broadur AE. Calcium homeosmsis in immobifizmim: an sxampls of rewxplive bypercalciuria. N Engl 1 Med lPSZ;%: 1136-l 140. 16 Gallagher JC, Rig@ BL, EismanI, Hamstra A, AmaudSB, DeLuca HF. lnrestitmlcalciumabsorp tion and serumvitamin D metabulitesin normal subjectsand asteoporoticpatients.J Cfin lmesl 1979:64:729-736.
P.
1983.
15Stewan
1985.
49
9(1990)49-57
133258
Lower mobility and markers of bone resorption in the elderly
Paul Lips, Floris C. van Ginkel, J. Coen Nztelenbos, Anje Wiersinga and Wim J.F. van der Vijgh
tmmobd~zation may lead 10 severe bone fox
Physical activily decreavr
might influence bone 10s~.We have evaluated the degree of mobility and
piti
age and lower mobility
parameters of bon turnover in
70 residents of a nursing home (mean age + SD St Y?9 years) and 68 residents of an afd peop+e’s fmme (mean age f SD 84 t 6 years). The mobility was asxsred with a standing and walking scow from 1 (severely disabled) to 5 (standingiwalking without help). When the subjects were anangd
acmding
to in-
neasing walking scrxe from I to 5. iarling urinary bydroxyprolinelcrealinine ratb gradually &creased IramX * 1910142 5~mollmmol (P
D concentrations with increasingwalking xore. Thezz dataindiutethat
lower mobility in the elderly leads to higher bone resorption. which may rupprrsdths forrnatmn of 1.2% dihydrwyvitamin
D.
Immobilization leads to increased bone resorption and bone loss. which may amount to as much as 1% per week 01 more than 30% in 6 months Il.:]; howwer atble!zs kave a higher bone mass ]3] and thus physical activity may prevent age-~.lated bone loss 14.51. Physical activity decreases with age and variation in mobility in the elderly might influence hone loss. Therefore, we have evaluated the degree of mobility and biochemical parameters of bone remodelling in elderly residents of twoinstitutions.
Carrespondence to. Dr P. UPS. Depl of EndocrinaloSy, P.O. Box 7057. X07 MB Amsterdam. The Netherlands.
Academisch Zekenhuis
0169.MM919ivSO3.5D Q IWO Elsevier Snence Publishers B V. (Biomedical Division)
“rije
“nwersitc,,.
50 Subjects and Methods This report is part of a greater study dealing with the effects of vitamin mentation
on vitamin
D status and parathyroid
were 70 residents of a nursing home. ‘Regina
or from their legal representatives. committee
of the university
10 men, mean age
‘De Kimme’ (56 wo-
+ SD 81 f 9 years) and 68 residents of an old people’s home, men, 12 men; 84 * 6 years). Informed
D supple-
function in the elderly 161. Subjects Pacis’ (60 women,
consent was obtained
from the participants
The study protocol was approved by the ethical
hospital. The residents of the old people’s home were
reasonably healthy and more or less active, but the nursing home residents suffered from cardiovascular. less mobile,
neurologfcal,
although
locomotor
not bedridden.
score, which has been used in Dutch score. standing and walking disabled) Table
and other chronic diseases and were
Physical ability institutions
was assessed with a mobility
for several years [7]. With
this
are graded according to a 5-point scale from 1 (severely
to S (able to stand/walk
easily without
1. The scores were obtained
help).
The score is presented
in
in a blind fashion shortly before or after the bio-
chemical studies. Urine
and blood samples were obtained in the nursing home in July and in the old
The subjects were fasted overnight. The first urine in
people’s home in September.
the morning was discarded. The subjects drank several glasses of water and the second urine, collected about 2 h later, was used for detemtination nine ratio (C&r). creatinine
renal phosphate threshold
ratio (Hp/Cr)
(TmP/GFR)
of calciumlcreati-
and hydroxyproline/
[8]. Fasting blood samples were obtained
the same morn-
ing and the plasma or serum were kept frozen until analysis. Serum and/or urine calcium, phosphate, bumin concentrations
were measured
calcium was corrected
for serum albumin
rected calcium
= calcium
was measured
by calorimetry
subject coefficient
HPLC (CPB)
lo-NO, were
(CV)
rum 1,25(OH),D
were 5 and 6%. concentrations
receptor as binding protein.
measured
(PTH(l-84))
volving aminoterminal
cor-
T [8]. The withinratio in a 2-h fast-
purification
by competitive
days) is 7.3%.
Se-
by a Sep-
was by a gradient mixture.
protein
Serum
binding
assay
The intra- and interassay coefficients
respectively.
The detection
of
limit was 3 nmoUI. Se-
were measured by CPB using chicken duodenal
The intra- and interassay CVs were 6 and 15%. respec-
tively. The detection limit is 10 pm&l
man PTH
with chloramine
Further
Serum
Hydroxyproline
column and a hexane-isopropanol
[9,10]. Vitamin
measured by single radial immunodiision index) was calculated
X 0.02 mmol/l.
D metabolites were chromatographed
using rat serum as binding protein.
variation
methods.
using the formula:
subjects on 4 non-consecutive
and eluted with ethanol.
concentrations
phosphatase and al-
laboratory
of the hydroxyproline/cmatinine
in 5 elderly
with a Nucleosil
25(OH)D
(g/l))
after oxidation
rum samples for analysis of vitamin Pak C I8 cartridge
alkaline
concentration
+ (40 - albumin
of variation
ing urine (measured
creatinine.
using standard
[ll].
D
binding protein (DBP) was
The free l,ZS(OH),D
as IOr x molar ratio 1,25(OH),D/DBP
[ll].
index (F-125 Serum intact hu-
was measured by a two-step immunochemical immunoextraction
followed
noassay. The intra-assay and interassay CVswere
method,
by a sensitive midregion 8.3 and 10.2%.
in-
immu-
respectively.
The
51 detection limit was 0.8 pm&l [12]. Serum osteocaltin concentrations were measured at the laboratory of Dr P. Dehnas (Lyon, France) by radiiimmunoassay using a rabbit antiserum against bovine osteocalcin and using kits obtained from ORIS Industrie, Gif SW Yvette, France. Statistical evaluation of the re~tts was made using the SPSSx program [13,14]. The data of the two institutions we-z combined and c-rahtated using analysis of variance (MANCVA) followed by orthogonal polynomial contrast analysis. According to this method, the biochemical data dassified into five groups on the grounds of mobility score were consecutively fitted to a linear or various exponential models, and the significance tested 1141.When the linear model is significant, the data in the five groups show a linear increase cm decrease with increasing mobility score. Biochemical determinants of the standing and walking scores were evaluated by stepwise multiple regression analysis.
Standing and walking scores in the nursing home and old people’s home residents are shown in Table 1. The biochemical parameters varied with ianeasing mobility scores, the results being similar for standing and walking scores. The biochemical results are arranged according to increasing walking score in Tables 2 and 3. T6e mean fasting urinary Ca/Cr and Hp/Cr showed a significant linear decrease within-
Table 1 Mobility score in 70 nursing home residents and 68 old people’s home residents Nursing home
old pwpi&
0 2. Able to stand up and remain standing with personal support 3. Able to stand up with personal support and remain standing with mechanical aid
0
4. Able to stand up and remain standing with difficulty and with/without aid
21
5. Can stand up and remain standing easily without help
1.
Cannot walk either with mechanical or with personal help
2. Able to walk between two
perronror with
one
person and B mechanical aid 3. Can walk with mechanical aid and rupervision (unsafe walkingpattern.
pcor balance)
4. Can walk a limited distance without supervision with/without mechanical aid (stain with help)
9. AL
:o nalk independently for a ;.T,‘~T distance an any surface in&dine: stirs
46
boms
Table 2 Results of 2 h fasting urine in nursing home and old people’s home residents grouped according to walking score Walking scare
n
C&r (mmollmmol)
HplCr (!.tmollmmol)
TmPiGf’R (mmolllj
1 2 3 4 5
15 17 33 3R 32
0.47 + a.43 0.54 * 0.42 0.44 * 0.35 0.33 f 0.23 0.29 t 0.22 P < 0.0.Y
31 f 19 29 * 22 24 * 12 18f 10 14 f 5 P 4 O.ixol’
0.89f0.20 0.74 f 0.14 0.84+0.17 0.83 f 0.19 0.88 ?: 0.15 NS
P < O.Olb
P < 0.001~
---
-
’ Overall significancebetween groups (MANOVA).
b Significanceof linearmodel (contrastanalysis);the expawttial models were not significant.
Table 3 Biochemical parameters of nursing home and old people’s home residents grouped according to walking score Walking score
n
1 2 3 4 5
17 17 33 39 32
1
2 3 4 5
17 17 33 39 32
Crcatinine
Albumin
(runON)
(pn)
Calcium’ (mm&l)
Pbasphate (mm&l)
35.4 * 4.0 38.2k3.1 39.4 t 3.6 40.2 * 3.2 42.6 f 2.5 P< O.wol~
2.41 f 0.12 2.34 f 0.09 2.27 f 0.09 2.36 * 0.08 2.26 * 0.08 P
1.12 f 1.02 * 1.03 f 1.05 * 1.04 f NS
P
PCO.mllb
52 * 28 %?21 93 * 23 89f 18 9of 19 NS
88*19 87+21 92231 92 + 62 81 f 22 NS
3.4 * 3.8 * 3.3 * 35 * 3.4 f NS
1.9 2.7 2.1 1.8 1.6
10 11 19 32 27
6.6 * 5.7 i 7.7 t 6.2f 6.1 *
0.14 0.15 0.15 0.13 0.13
1.5 I.5 2.4 1.8 1.5
P
Walking score
n
zs(G:i)u (nmolil)
135(OH)zD (PnlOku
1 2 3 4 5
17 17 33 39 32
22.2 * 22.6 + 24.6 + 22.5 + 25 5 + NS
56237 65 * 29 79+34 78 * 24 95 * 26 P < o.cw
P < 0.02*
0.8Bf 0.58 1.03 f 0.46 1.24 f 0.47 1.19f0.36 1.39fO3-i P < O.W5’
P<0.001b
P < O.Olb
P< 0.001~
7.7 7.2 12.1 12.5 12.1
’ Overall significancebetween groups (MANOVA) b Significanceot linearnodei (contrastanalysis). ’ Conccted 6x swum albumin.
DBP (mwl) 330 f 327 * 329 * 342 f 355 *
F-1.25 index (molar ratiox loI) 38 20 3n 46 31
53
creasing walking score. Individual values for these parameters are shown in Figs. 1 and 2. The mean values for urinary Hp/Cr were. increased with walking scores 1-3, and in the normal range with walking scores 4 and 5. Serum albumin showed a linear increase with increasing walking scores. The serum calcium mocentration, carrected for semm albumin, decreased significantly in a !&ear way with increasing walking score. Individual values of serum calcium arc shown in Fig. 3. The serum conanr~atiorls of creatinine, phosphate, alkaline phosphatase, FTH(l-fN) and 25(OH)D did not change significantly with increasing walking score. The serum osteocalcin concentration showed a significant change with increasing walking score, but the relationship was non-linear with the highest value at walking score 3. The sexurn concentrations of 1,25(OH),D and DBP and the F-1,25 index showed a significant linear increase with increasing walking snore. Individual values of serum 1,25(OH)JI are shown in Fig. 4. There was a significant negative correlation between strum calcium and serum 1,25(OH)@ (r = -O.z?Jl,P -=z0.001). The mobility scores were lower in the nursing home than in the old people’s home. The mean fasting urinary Hp/Cr ratio was higher (Pc 0X01), and the scram albumin and 1,25(OH),D concentrations were lower (P c 0.001 and P < 0.02, respcctively) in the nursing home residents than in the residents of the old people’s home [6]. The other biochemical parameters were similar in the two instituticms. Because of these differences, the two institutions were also considered separately.
54 The mean fasting HplCr ratio decreased from 31 & 19 to 21 f 12~moUmmol with increasing walking score (l-4) in the nursing home residents (P = 0.17, NS), and from 21 + 11 to 14 + 5 ~moUmmo1 with increasing walking score (3-5) in the old people’s home (P < 0.05). The serum albumin concentration increased from 35.4 & 4.0 to 40.1 2 3.5 g/l with increasing walking score in the nursing home (P c O.OOS) and from 40.2 + 3.0 to 42.6 f 2.5 gA with increasing walking score in the old people’s home (Pc 0.01). The serum l,ZS(OH),D concentration increased with increasing walking score in both institutions, but the increase was not significant. Serum 1,25(OH)zD increased with increasing standing score in the old people’s home from 77 ? 27 to 93 + 26 pmolfl (P c 0.05). Biochemical determinants of the walking score were assessed with stepwise multiple regression analysis. The most important single determinant was serum albumin (multiple R' = 0.28, P < 0.001). When including urinary Ca/Cr (P c 0.001) and serum 1,2S(OH),D (P 5 0.02) in the regression analysis, the multiple RZ increased to 0.44. When the residence of the subjects was taken into account, this was included in the first step (P< O.OOl), the following steps being albumin (P < 0.001) and urinary CalCr (P < 0.02) leading to a multiple R* = 0.55. When assessing the determinants of the standing score, the following parameters were included in the
t
.
Hp/Cr
ratio in residents of a nursing home and old people’s home grouped according lo walking xore. The dotted line indicates the upper refer-
Fis. 2. Individualvaluer of fastingurinaryhydroxyprolinekrcatininc ence limit.
55
calcium .
2.60t -
.
.
:
I -!-
2.40. -
; i _1 f, -i li f
.
--
-T-
: 220 :
f.
c
.
FQ. 3. Individual values of serum calcium (corrected for serum albumin) in resklen~ of a musing imme and old people’s home grouped according to walking score.
1,25(OH),D
1
1
*
3
4 w.king
5 -
Fig. 4. Individual values of serum 1,ZSdihydmx)ritamin D in residents of a ntig home acd old people’s home grouped according to walking so%. ‘l%e doned line indicates the lower reference limb in healthy adults
56 regression analysis in this order: residence (P < O.OOl), urinary HplCr (P c 0.02) and albumin (P < 0.05) leading to a multiple R’ = 0.69.
Discussion Complete immobilization, such as after spinal cord injury, leads to severe bone loss [I]. The effects of partial immobility or lower physical activity are less well known. Physical activity decreases with age and the degree of mobility varies with the residence. Elderly at home or in an old people’s home are usually more mobile and active than geriatric patients in a hospital or a nursing home. The subjects in thii study were more or less healthy inhabitants of an old people’s home and residents of a nursing home, comprising all mobility degrees as is visible from the walking scores. Lower mobility, i.e., low walking score, was associated with higher valuesof serum calcium concentration and fasting urinary calcium and hydroxyprotine excretion, reflecting increased bone resorption. The relatively higher serum calcium conccntration apparently suppressed the formation of 1,25(OH),D, as has been reported during immobilization [15]. This suggests that, in addition to decreased renal function, lower mobility could contribute to the low serum 1,25(OH)P concentration and lower calcium absorption in the elderly [16]. The lower serum 1,25(OHhD in the relatively immobile elderly (walking score l-3) cannot be explained by impairment of renal function, as the serum creatinine concentration was similar in all mobility groups. We would also have expected a lower serum PTH(l-84) in the immobile elderly than in the more active groups, but a relative decrease may have been masked by stimulation of the parathyroid glands by vitamin D deficiency or decreased renal fmtction 14. Since the nursing home residents had lower walking scores and more chronic diseases than the residents of the old people’s home, the increased bone resorption could be attributed to chronic diseases. However, the fasting urinary Ca/Cr ratio was not significantly different between the two institutions [6], but varied significantly with the walking score (Table 2). When considering the two institutions separately, significant changes of the biochemical parameters with the mobility score were also found. Of course, the residence, the degree of mobility and general state of health are closely interrelated, which is reflected by the fact that residence, serum albumin and urinary CalCr ratio are the best prediitars of the walking score according to stepwise multiple regression analysis. Our data suggest that relative immobility is an important factor in bone resorp tion and bone loss in the elderly. However, a definite conclusion cannot be drawn from this cross-sectional study. A further prospective dudy should be performed to determine whether improving the walking score leads to a decrease of bone resorp tion parameters and an increase of the serum 1,25(OH),D concentration.
Acknowledgements We are indebted to participants and personnel of ‘Regina Pacis’ and ‘De Kimme’,
57
to Drs M. Hermans, C. Leering and A. van der Hogen, to MR E. Lommerse and Mr G. Hobson for their help in the study, to the labozzary of Clinical Chemistry, to Mr S. Kuipet for vitamin D metabolic measurements. ro Dr R. Bouillon (University of Leuven) for the estimation of DBP and to Dr P. Delmas (Lyon, France) for the estimation of osteocalcin. This study was supported by the Praeventiefonds. The Hague.
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