Effect of prolonged bed rest on bone mineral

Effect of Prolonged Bed Rest on Bone Mineral By CHARLESL. DONALDSON,STEPHEN B. HULLEY, JOHN M. VOGEL, ROBERT S. HATTNER, JON H. BAYERSAND DONALDE. MCMILLAN Three healthy adult males were restricted to complete bed rest for periods of 3036 weeks. Urinary calcium excretion was elevated throughout bed rest, averaging 61 mg./day above the base-line value of 193 mg./day. Maximum urine calcium excretion occurred during the seventh week and was 136 mg./day above the base-line value. Fecal calcium excretion was also increased during bed rest. Sweat calcium was unchanged and represented only 2 per cent of calcium output. Mean calcium balances for the three subjects during bed rest were - 202, -207, and -254 mg./day. The measured calcium loss during the entire bed rest period averaged 4.2 per cent of the estimated total body calcium. Calcium balance became more normal but remained negative during the three-week period of reambulation. Phosphorus excreted in the urine and phosphorus balance patterns were

similar to calcium patterns. Serum calcium and phosphorus levels did not change appreciably during bed rest, but both levels feIl during reambulation. Urinary hydroxyproline and pyrophosphate were mildly elevated during bed rest and fell with reambulation. Gamma ray transmission scanning of the OScalcis revealed huge losses of mineral during bed rest. The decreased mass in the central portion of this bone ranged from 25 per cent to 45 per cent. Mineral reaccumulated in the central OS calcis following reambulation at a rate similar to its rate of loss during bed rest. Bone dissolution during bed rest may occur to a greater extent in weight-bearing bones than in the remainder of the skeleton, and tbe process appears to be reversible. (Metabolism 19: No. 12, December, 1071-1084, 1970)

ONE MINERAL is lost during immobilization. This disuse osteopenia occurs locally in patients with fracture1 or hemiplegia” and is generalized in quadriplegia. 3 An increased rate of calcium excretion has been shown jn

R

From the Metoholic Unit, Department of Medicine, and the N&ear Medicine Service, 1’3. Plchlic Health Service Hospital, San Francisco, Calif. Received for publication May 7, 1970. This investigation was sapported by National Aeronautics and Space Administration Ccmtract T-58941. CHARLES L. DONALDSON, M.D.: Chief, Endocrine-Metabolic Service, U.S. Public Health Service Ho.vpital. San Francisco, Calif.; Assistant Clinical Professor of Medicine, Vniversir) of California Medical Center, San Francisco, C&f. STEPHEN B. HLJLLEY, M.D.: Director, Metabolic Unlit. U.S. Public Health Service Hospital, San Francisco, Calif.; Clinical Instructor of Medicine. University of California Medical Center, San Francisco, Calif. JOHN M. VOGEL, M.D.: Chief, Nuclear Medicine Service, U. S. Pltblic He&h Service Hospital, San Francisco, Calif.; Associate Radiologist, Nuclear Medicine, University of California Medical Center, Sun Francisco, Calif.; Assistant Clinical Professor, Nuclear Medicine, Stanford University Medical Center. Palo Alto, Calif. ROBERT S. HATTNER, M.D.: Department of Medicine. Unil,ersity of California School of Medicine, San Francisco, Culif. JON H. BAYERS. M.D.: Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, Calif. DONALD E. MCMILLAN, M.D.: Director of Diabetes Research, The Sansam Clinic Rcsrarch Foundation, Santa Barbara, Calif. MFTAHOLISM. VOL. 19, No. 12 (DECEMBER),

1970

107I

1072

DONALDSON ET AL.

patients immobilized by fractures~~z or paralysis3rF-s and also in normal individuals whose activity is reduced by bed rest. g-14 Calcium balance measurements in normal subjects during bed rest for up to 7 weeks have shown the rate of loss to be 0.4 per cent13 and 0.6 per centlo of total body calcium per month, although greater rates were seen at the end of the latter study. X-ray measurements of the heel have suggested a much larger rate of mineral 1oss,12 but the ability of x-ray densitometry to distinguish between bone and soft tissue changes has been questioned .lB Recovery of mineral when normal activity is resumed has not been adequately demonstrated”JG,lT and in one study was incomplete for as long as 14 years.l The current investigation was undertaken to examine the possibility that larger rates of mineral loss might be seen during bed rest of longer than 7 weeks, the possibility that bone dissolution occurs preferentially from weight-bearing bones during bed rest, and the degree of remineralization that occurs during reambulation. Mineral metabolism was studied by calcium and phosphorus balances. A gamma ray transmission scanning technic designed to be unaffected by soft tissue was used to measure changes in calcaneus mineral content during bed rest and reambulation. MATERIALS AND METHODS

Study Subjects Three healthy male volunteers, ages 21-22 years, underwent 30 (G.B.) and 36 (C.S., R.R.) weeks of continuous bed rest. Balance data obtained during bed rest were compared with those of 3-week ambulatory periods before and after. At least 1 week of equilibration on the study diet was allowed before beginning the balance. During the base-line ambulatory period, the subjects engaged in a normal level of activity suppIemented by thirty minutes twice daily of treadmill walking at 3 miles per hour up a 6’ grade. During bed rest the subjects remained under close supervision in bed or on a wheeled stretcher. Freedom of horizontal movement was permitted in bed, and the subjects raised themselves on one elbow for eating and reading. They were not allowed to sit up or dangle their legs over the bed, and defecation and micturition were performed while supine. Daily weights were obtained using an in-bed scale (Acme).

Balance Diet The whole food diet was composed of seven daily menus, each consisting of three meals and an evening snack. All foods except for some staples, soft drinks, and meats, were purchased in common lots prior to the study to assure maximal constancy. Fresh fruits were avoided and canned whole milk and frozen homogenized eggs were used. Distilled water was used for food preparation, drinking, and utensil cleansing. The subjects were required to eat all the food, lick their plates clean and drink a distilled water rinse of their glassware. Dentrifice used by the subjects was free of mineral except silica. Dioctyl sodium sulfo-succinate (Colace) was administered during bed rest for constipation. Analyses of the diet were obtained at three intervals during the study by preparing an additional serving of each menu for 1 week. The meals were pooled daily, homogenized, and an aliquot was stored for mineral analysis. The results of these analyses are compared to the calculated dietary contents in Table 1.

Serum, Stool and Urine Collections Thirty-five milliliters of blood were drawn in the fasting state on the first day of each 7-day period and the serum stored frozen at -22% A 5-per cent aliquot of each day’s urine was acidified with 1 ml. of 12 N HCl per 100 ml. of urine and was stored at 4OC.

I073

BED REST AND BONE MINERAL

Table l.-Dietary D;Y

D;Y

Calcium (mg.) Phosphorus hfagnesium

899 (10) (mg.) 1351 (69) (mg. ) 202

(6) Nitrogen

(Cm. 1

Potassium

(mEq.)

Sodium (mEq.) Calories

14.4 (1.2) 68.2 (5.1) 158.8 (5.4) -

D;Y

Composition -~

Measured D;Y D;Y

._ D;Y

861 885 937 911 971 893 (91) (17) (6) (50) (17) (43) 1336 1476 1511 1361 1505 1415 (39) (20) (32) (57) (32) (9) 231 227 229 226 208 213 (4) (12) (3) (4) (6) (14) 13.7 15.3 14.4 13.4 13.0 14.4 (0.6) (0.2) (1.5) (0.7) (0.8) (0.5) 74.0 73.6 64.1 64.8 63.8 72.4 (3.2) (6.4) (7.3) (3.3) (3.9) (4.9) 147.8 150.0 156.8 165.3 155.6 176.0 (6.2) (3.3) (6.5) (9.8) (16.2) (6.4) -

-~

* Mean values from in parentheses.

Day 6

three duplicate

determinations

.~~~_..~~_

7-Day MC%Xl

908 (16) 1422 (20) 219 (6) 14.1 (0.5) 68.7 (4.4) 158.6 (6.9) -

Predicted ‘I-Day Mean

950 1 390

256 13.9 69.4 155.3 2108

.____. ~~_~

are shown with standard

deviation

At the end of the 7-day period the specimens were pooled and a one-week aliquot stored at -22’C. Pyrophosphate was determined weekly on an aliquot of a fresh unacidified 24hour specimen, and a second morning urine was examined for microscopic crystals each week. A stool marker (100 mg. brilliant blue) was administered by mouth at the beginning of each 7-day period. The stools for that period were collected from the first appearance of the marker in the stool until the appearance of the subsequent marker. Stools were collected in bedpans lined with mylar film and were subsequently transferred with distilled water rinsing into epoxy-lined one-gallon canisters and refrigerated. Upon completion of the 7-day collections, the stools were further diluted with distilled water and 300 ml. glacial acetic acid to a final weight approximately three times the initial weight. They were homogenized for 30 minutes on a paint shaker, and an aliquot was stored at -22OC for subsequent ashing. Sweat

Collections

Forty-eight-hour collections were used to estimate weekly cutaneous mineral losses. The collections began by thoroughly washing each subject with 0.1 per cent acetic acid to remove residual cutaneous mineral. Pajamas and linen which had been rinsed in distilled water were used during the collection period, and washing and skin care were discontinued. After 48 hours, the entire body was washed again with 0.1 per cent acetic acid, pajamas and linen were similarly treated, and all rinsing solutions were collected. Two and one-half liters of the collected 22 L. were evaporated to dryness and reconstituted in 30 ml. of 1 N HCl. A control set of linen and pajamas was similarly treated each week to correct for residual mineral.

Ashing

of Stool and Diet

Muffle furnace ashing was used to prepare samples for calcium and phosphorus determination. These values were verified by digesting additional aliquots of all samples in sulfuric acid for phosphorus analysis and in nitric acid for calcium analysis, For the muffle furnace ashing, a weighed aliquot of diet or stool homogenate (approximately 20 Cm.) was ashed in a covered crucible at 575°C for 72 hours and the residue reconstituted with HCl. Recovery of added calcium was 98.8 ? 3.1 per cent (SD) and that of added phosphorus 98.4 f 2.7 per cent (SD). Sulfuric acid digestion was performed by adding 20 ml. of concentrated sulfuric a&i

DONALDSON

1074

ET AL.

Fig. l.-Lateral section of OS calcis showing area assessed by gamma ray transmission scan (outlined by the heavy black line). Serial scan passes were performed at levels indicated by horizontal lines.

CALCIUM

400

-

200

-

BEDREST

mg/day IOO0 IIOO-

-

1000

\

URINARY

“\

________________

PHOSPHORUS mg /day

000‘“-? 7000

0

07 Fig. Z.-Effect

4

8

12 WEEKS

16

20

24

28 024

of prolonged bed rest on urinary calcium and phosphorus excretion. of the weekly values for three subjects is plotted. Range of observations is shown by vertical lines.

Mean

BED REST

AND BONE

MINERAL

.i

i2

16

i0

WEEKS

(GB,

BEDREST

1200

1

2’4

28

i2

h 07

07

r-l J +IOO

--SWEAT li

1000

,“,&e-

CALCIUM OUTPUT

2’4

2b’ 07

- 300 _200 CALCIUM _,oo BALANCE

!-.__-A

!--I-a_

000

2b

WEEKS

OF-3

dietary

li

-_____

I-b-“rC_*..

________”

a-.,--

______..

“_

---.

1 0

Rl.J/d0Y

FECAL

600

A-l-

-SWEA1

0 0

4

0

I2

16

20

24

26

32

36

Fig. 3.-Effect of prolonged bed rest on calcium balance in subjects R.R., G.B. and C.S. Calcium output by way of sweat, urine and stool is plotted cumulatively on ordinate; time is shown on abscissa. Mean calcium intake was 908 mg./day; calcium balance is shown on right-hand scale. and three selenized granules (11 mg.) to a weighed aliquot of homogenate (approximately 4 Gm.). The suspension was boiled for 2 hours and diluted to 100 ml. with distilled water. Recovery of added phosphorus was 100.4 f 2.4 per cent (SD). Nitric acid digestion was performed in a similar manner employing 10 ml. of 90 per cent HNO, and boiling until l-2 ml. remained (about 5 minutes). Recovery of added calcium was 99.0 i 1.1 per cent (SD).

70.4

66.2

114

63.5

108

63.4

111

-98

1.520

569

951

1422

-359

1267

22

990

247

908

+49

1328 +94

64.8 60.0

115

1373

595

118

946 427

733

1422

-129

-247

1422

23 1037

782

1155

232

36

964

908

155

908

17

819

281

90s

58.9

111

+7

1415

411

1004

1422

-209

59.0

107

-4

1426

400

1026

1422

-200

1108

34

833

241

908

G.B.

60.6

126

+229

1193

342

851

1422

-131

1039

34

790

215

908

63.7

105

+3

1419

593

826

1422

- 121

1029

17

828

184

908

base-line

Data*

during

59.5

109

+I7

1405

402

1003

1422

-192

1100

24

855

221

908

2.-Metabolic

1117

Table

* Mean values for each of three subjects (G.B., R.R. and C.S.) are shown (Reamb) periods. Bed rest is subdivided into three consecutive intervals.

(ml./min.)

111

-19

-84

Total

Balance

clearance

1441

1506

1300

+122

Stool

Creatinine

946

495

999

507

877

423

Urine

OUtQUt

Intake

1422

-201

+15

PhosQhorus

1422

-203

20

1109

D

893

sweat

Total

1422

24

1111

806

Balance

260

827

283

163

908

706

908

urine

908

R.R.

stooi

output

(m&/day)

Calcium

Intake

(weeks)

(mg./day)

Period Duration

Subject

--____

60.7

111

-64

1486

540

946

1422

-241

1149

20

876

253

908

ambulatory

62.3

114

-46

1468

483

985

1422

-169

1077

13

782

282

908

64.7

110

+58

1364

481

883

1422

-78

986

21

172

193

908

62.5

113

-41

1463

467

996

1422

-193

1101

17

802

282

908

61.1

109

-29

1451

478

973

1422

-214

1122

26

845

251

908

61.1

110

-32

1454

496

958

1422

-253

1161

19

912

230

908

62.4

117

+I67

1255

477

778

1422

-160

1068

28

865

175

908

bed rest (Bed) and reambulatory

61.7

107

+179

1243

494

749

1422

-102

1010

15

840

155

908

(Amb),

60.5

111

-13

1435

516

919

1422

-210

1118

883 12

223

908

E

5

RED REST ANDBONE

MINERAL

BEDREST I

SERUM CONCENTRATION

6 PHOSPHORUS

mg/l00ml

/ 0

4

8

I2

OFF-J

16

20

24

28 OFF-i

WEEKS

Fig. 4.-Effect of prolonged bed rest on serum calcium and phosphorus concentration. Mean of weekly values for three subjects is plotted. Range of observation\ i\ Lhown by vertical

lines.

Laboratory Determinations Calcium was determined by atomic absorption spectrophotometry on an ~u~omaied Perkin-Elmer Model 303.18 Phosphorus was analyzed by the Technicon Autoanalyzer adaptation of the Fiske and SubbaRow method’s using standards adjusted to the pH of rhe samples. Urine and serum creatinine concentrations were determined using the Technicon ,4utoanalyzer adaptation of the Folin Wu method.20 Hydroxyproline was determined by I he method of Kivirikko and Prockop,21 and pyrophosphate was analyzed by a modification of the method of Fleisch and Bisaz.22 All methods were initially validated by recovery \rudies, and quality control was maintained by including standard sera in all runs. All :rssays were carried out in duplicate and the results accepted only when the disparity w:~\ less than 3 per cent (calcium, phosphorus and creatinine) or 5 per cent (hydroxyproline). Vitrogen, sodium, potassium, and magnesium balance data were obtained, as well a\ psychiatric, biometric, and fluid compartment analyses. For further details on these studies I he reader is referred to the complete technical report.“” A method for assessing the mineral content of the central OS calcis became avarIable XI the 12th week of bed rest. The modification of Cameron’s technic”4 for 1’51 gamma trammission scanning has been previously described.‘“.“” Correction for changes in the soir tissue of the heel was provided by surrounding the area of the heel to be scanned with ;t [Issue-equivalent material of fixed dimensions. The values obtained on nine serial scan pa5~c, .I[ 1 (‘X-inch intervals through the central OS calcis (Fig. 1) are summed to provide .I ~XJYUI-C srf the bone mineral content. RESULTS

Calcium Metabolism During bed rest, mean urinary calcium excretion rose from an average bascline value of 193 mg./day to a maximum of 329 mg./day in the seventh week I Fig. 2). The value subsequently fell but did not return to the base-line level until reambulation. The mean increment in urinary calcium excretion during the entire bed-rest period was 61 mg./day. Calcium balance data for the three subjects are shown in Fig. 3 and Table 2. Mean calcium balance during base-line ambulation was 78 mg./day anti

DONALDSON

Fig. L-Effect of prolonged bed rest on phosphorus and C.S. Mean phosphorus intake was 1422 mg./day.

during bed rest was -220 the mean calcium balance

mg./day.

During

ET AL.

balance in subjects R.R., G.B.

the first 3 weeks of reambulation,

was - 160 mg./day. For the two subjects whose observations extended into subsequent weeks, a further trend toward positive balance was seen. For each subject, fecal calcium excretion increased during bed rest and a more negative mean calcium balance was observed during bed rest than during the base-line ambulatory period. Mean calcium loss by way

BED REST AND BONE MINERAL

I 1

BEDREST

I

PYROPHOSPHATE

URINARY HYDROXYPAOLINE mg/doy

4o

MEAN

CONTROL

30

0 0;4

4

8

12 WEEKS

I6

20

24

28 OT

Fig. 6.-Effect of prolonged bed rest on urinary hydroxyproline and pyrophosphate excretion. Mean of weekly values for three subjects is plotted. Range of observations is shown by vertical lines.

of the integument was 2 per cent of the total calcium output and was not appreciably altered by bed rest. The total loss of calcium for the subject undergoing 30 weeks of bed rest was 42.4 Gm., and for those undergoing 36 weeks it was 64.1 and 52.1 Gm. Mean serum calcium concentration was 9.96 mg./lOO ml. during baseline, 9.81 mg./lOO ml. during bed rest, and 9.35 mg./lOO ml. during reambulation (Fig. 4). Phosphorus Metabolism Mean urinary phosphorus excretion was higher throughout the period of bed rest than during the base-line period in all three subjects. The mean increment was 93 mg./day (Fig. 2). During reambulation, the values fell abruptly to a mean level of 105 mg./day below baseline. Phosphorus balance data are shown in Fig. 5 and Table 2. Bed rest did not cause consistent changes in fecal phosphorus excretion. Mean phosphorus balances were $58 mg./day during base-line ambulation, -34 mg./day during bed rest, and + 167 mg./day during reambulation. There was no clear change in serum phosphorus concentration during bed rest. A slight decrease was seen during reambulation (Fig. 4). Cutaneous phosphorus loss was too low to measure (less than 1 mg./day). Hydroxyproline

and Pyrophosphate

Mean urinary hydroxyproline excretion was 42.9 mg./day during base-line ambulation, 46.4 mg./day during bed rest, and 40.7 mg./day during reambulation (Fig. 6). The mean urinary pyrophosphate pattern was similar: excretion was 3.05 mg./day during base-line ambulation, 3.70 mg./day during bed rest, and 2.35 mg./day during reambulation (Fig. 6). For both of these substances.

1080

DONALDSON

0:

I

0

1

12

I

,

I

24 WEEKS

I

36 SINCE

ONSET

r

I

I

48 OF

I

60

I

I

ET AL.

I

72

BEDREST

Fig. 7.-Loss of bone mineral content of central OS calcis during bed rest and recovery during reambulation. For each point, sum of values obtained on 9 serial scan passes at %-inch intervals are expressed as per cent of initial sum. Arrows indicate point of reambulation for G.B. (triangles), R.R. (circles) and C.S. (squares). Closed symbols represent bed rest and open symbols represent reambulatory values.

as was the case with urinary calcium, the highest values were seen during the seventh week of bed rest. OS Cal& Mineral Content

The changes in bone mineral content of the central OS calcis subsequent to the 12th week of bed rest are shown in Fig. 7. There was a decline in bone mineral during bed rest for all three subjects. The per cent loss from the 12th through 36th weeks of bed rest was 44.5 per cent for C.S. and 33.3 per cent for R.R. The per cent loss for G.B. during the 12th through 30th weeks of bed rest was 25.1 per cent. During reambulation, all three subjects regained OS calcis mineral at a rate similar to the rate of loss during bed rest and in each case exceeded the initial value. Additional Observations

All three subjects lost weight during bed rest and gained during reambulation (Table 2). There were no consistent changes in creatinine clearance (Table 2) during the study and weekly inspection of urine sediment revealed no evidence of crystalluria. No significant morbidity occurred during bed rest. Pedal edema and marked tenderness of the soles of the feet developed upon reambulatmg and persisted 3-4 weeks.

BED

REST

AND

BONE

IOX1

MINERAL

DISCUSSION

The mean absolute loss of calcium for the three subjects in this study during bed rest was 1.54 Gm./week. Because the total body calcium of these subjects is estimated to be 1250 Gm.,27 the mean loss during bed rest was approximately 4.2 per cent of the body calcium store, an average rate of 0.5 per cent per month. Urinary calcium showed a definite pattern, reaching a maximum 70 per cent above base line at the seventh week of bed rest and subsequently stabilizing at about 30 per cent above base line. Fecal calcium was elevated throughout bed rest, and no trend toward a diminution of the negative calcium balance was observed during this period. The two previous balance studies of healthy subjects at bed rest”‘.‘:: differ from the current study in three design features: lower body casts were employed, the subjects were permitted out of bed for 30 minutes daily, and bed rest did not exceed 7 weeks. In spite of these differences, the calcium loss rate was similar: 0.4 per centl” and 0.6 per centlO per month.* The current study is the first to extend observations beyond 7 weeks, and shows that loss of calcium continues for at least 36 weeks at a similar rate. During reambulation, calcium and phosphorus balances tended to become more positive. This change was moderate in the case of calcium, and the balance remained negative during the first few weeks of reambulation. This observation has been previously reported5Jo but is surprising in view of the rapid fall in serum and urinary calcium, and the increase in OS calcis mineral during this period. The increase in phosphorus balance during reambulation was dramatic, suggesting phosphate assimilation in areas other than bone, such as muscle. This hypothesis is supported by the observed increases in body weight, and in nitrogen balance.Z:’ The total body skeletal loss of 4.2 per cent found by calcium balance contrasts with the loss of bone from the OS calcis. Direct measurements of the central OS calcis mineral content beginning in the 12th week of bed rest demonstrated a mean decrease of 34 per cent during the ensuing 18-24 weeks. These disproportionate losses, as well as subsequent data on other bonesZR suggest that weight-bearing bones contribute a major portion of the mineral lost durjn, bed rest. Recovery of OS calcis mineral began upon reambulation. The rate of rcmineralization was similar to that of loss, and all subjects had exceeded the initial value by the 36th week. Although disuse osteopenia is generally considered to be fully reversible, this has not previously been documented. In one comprehensive study of femoral fractures, the mineral content of the ipsilateral tibia was not completely regained even after as much as 14 years of normal activity.’ Several authors have emphasized that evidence for the occurrence of remineralization has not been available in the past.5,1’;,1i Under the current study conditions which may differ from fractures, disuse osteopenia is clearly a reversible phenomenon. Estimation of cutaneous mineral losses, only occasionally attempted in the past. has yielded conflicting results.‘“J” Because sweat mineral loss might reason+ Calculated from the published data assuming total body calcium to he 1250 Gm.

1082

DONALDSON ET AL.

ably be expected to vary with the degree of physical activity, it was important to determine the magnitude of mineral excretion by this route in the current study. Calcium recovered from skin averaged 2 per cent of the total calcium output, and no phosphorus was detected, as previously reported.“r No consistent change in mineral loss by this route was observed when bed rest values were compared with those during ambulatory periods. These data confirm the lower previous estimate of sweat calcium contenFg and suggest that cutaneous mineral losses may be ignored in studies of this type. No crystalluria or evidence of ureteral stone formation was observed in spite of the higher levels of urinary calcium and phosphorus during bed rest. In this regard, the increased fluid intake and output,“” as well as the increased excretion of pyrophosphate (an inhibitor of crystal formation3”), may have exerted a protective influence. The mechanism for the loss of bone mineral during bed rest is uncertain.g,33 Parathyroid hormone may play a role, because disuse osteopenia apparently does not develop in parathyroidectomized animals.34 However, from changes in calcium metabolism in paralyzed humans, Heaney has concluded that parathyroid hormone levels are depressed. G The high urinary and fecal excretion of calcium seen in the current subjects supports Heaney’s concept, but the increased clearances of phosphate do not. Direct measurements will probably be necessary to clarify the role of parathyroid hormone and other humoral agents in this condition. Classically, disuse osteopenia has been thought to be due to mechanical factors: either to absence of pressure transmitted to bone, or to absence of tension applied to bone by muscle, or both. zr, Quiet standing for 2 or more hours per day appears to reverse the changes in mineral metabolism induced by bed rest 14s3&and vigorous supine exercise for as long as 4 hours daily is probably inef;ective.14J7 Evidence of this type supports the concept that it is the absence of pressure forces on the skeleton which is primarily responsible for disuse osteopenia, possibly by altering piezoelectric forces within the bone.38 This local mechanism provides the most reasonable basis for the disproportionate mineral loss from a weight bearing bone observed in the current investigation. ACKNOWLEDGMENTS The authors acknowledge the valuable assistance of Milton 2. Nichaman, M.D., for staff support; G. Donald Whedon, M.D., for consultation; William M. Smith, M.D., for administrative support; Miss Suzanne Thornley, Miss Kathleen Jo and Mrs. Janet Mooney and their respective nursing, laboratory and kitchen staffs; Mrs. Marian Kolb for bone scanning; and Mrs. Audrey Cathrell, Miss Edna Indritz and Mr. Jerry1 Price for typing, illustrations and photography.

REFERENCES 1. Nilsson, B. E. R.: osteoporosis. Acta Orthop. 1966. 2. Hodkinson, H. M., and in Unilateral osteoporosis hemiplegia in the elderly. J. Sot. 15:59, 1967.

Post-traumatic Stand. 91: 1, Brain, A. T.: longstanding Amer. Geriat.

3. Whedon, G. D., and Shorr, E.: Metabolic studies in paralytic acute anterior poliomyelitis. II. Alterations in calcium and phosphorus metabolism. J. Clin. Invest. 36: 966, 1957. 4. Howard, J. E., Parson, W., and Bigham, R. S.: Studies on patients convalescent

lOK3

BED REST AND BONE MINERAL from fracture. Bull. Johns Hopkins Hosp. 77:291, 1945. 5. Rose, G. A.: Immobilization osteoporosis. A study of the extent, severity, and treatment with bendrofluazide. Brit. J. Surg. 53:769, 1966. 6. Heaney, R. P.: Radiocalcium metabolism in disuse osteoporosis in man. Amer. J. Med. 33:188, 1962. 7. Dunning, M. F., and Plum, F.: Hypercalciuria following poliomyelitis: its relationship to site and degree of paralysis. Arch. Intern. Med. (Chicago) 99:716, 1957. 8. Klein, L., van den Noort, S., and DeJak, J. I.: Sequential studies of urinary hydroxyproline and serum alkaline phosphatase in acute paraplegia. Med. Serv. J. Canada 22: 524, 1966. 9. Birge, S. J., and Whedon, Hypodynamics and Hypogravics. Academic, 1968, p. 213. 10. Deitrick, J. E., Shorr, E.: Effects of various metabolic and of normal men. Amer.

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