Skip Navigation LinksHome > February 2002 - Volume 34 - Issue 2 > Shorter, more frequent mechanical loading sessions enhance b...
Medicine & Science in Sports & Exercise:
CLINICAL SCIENCES: Clinical Investigations

Shorter, more frequent mechanical loading sessions enhance bone mass

ROBLING, ALEXANDER G.; HINANT, FELICIA M.; BURR, DAVID B.; TURNER, CHARLES H.

Free Access
Article Outline
Collapse Box

Author Information

Department of Anatomy and Cell Biology; Department of Orthopaedic Surgery; Biomechanics and Biomaterials Research Center; Indiana University School of Medicine, Indianapolis, IN

Submitted for publication February 2001.

Accepted for publication May 2001.

Collapse Box

Abstract

ROBLING, A. G., F. M. HINANT, D. B. BURR, and C. H. TURNER. Shorter, more frequent mechanical loading sessions enhance bone mass. Med. Sci. Sports Exerc., Vol. 34, No. 2, pp. 196–202, 2002.

Purpose: The beneficial effects of exercise on bone mass and strength can be attributed to the sensitivity of bone cells to mechanical stimuli. However, bone cells lose mechanosensitivity soon after they are stimulated. We investigated whether the osteogenic response to a simulated high-impact exercise program lasting 4 months could be enhanced by dividing the daily protocol into brief sessions of loading, separated by recovery periods.

Methods: The right forelimbs of adult rats were subjected to 360 load cycles·d−1, 3 d·wk−1, for 16 wk. On each loading day, one group received all 360 cycles in a single, uninterrupted bout (360 × 1); the other group received 4 bouts of 90 cycles/bout (90 × 4), with each bout separated by 3 h. After sacrifice, bone mineral content (BMC), and areal bone mineral density (aBMD) were measured in the loaded (right) and nonloaded control (left) ulnae using DXA. Volumetric BMD (vBMD) and cross-sectional area (CSA) were measured at midshaft and the olecranon by using pQCT. Maximum and minimum second moments of area (IMAX and IMIN) were measured from the midshaft tomographs.

Results: After 16 wk of loading, BMC, aBMD, vBMD, midshaft CSA, IMAX, and IMIN were significantly greater in right (loaded) ulnae compared with left (nonloaded) ulnae in the two loaded groups. When the daily loading regimen was broken into four sessions per day (90×4), BMC, aBMD, midshaft CSA, and IMIN improved significantly over the loading schedule that applied the daily stimulus in a single, uninterrupted session (360×1).

Conclusion: Human exercise programs aimed at maintaining or improving bone mass might achieve greater success if the daily exercise regime is broken down into smaller sessions separated by recovery periods.

The crucial role of physical activity in the acquisition and maintenance of bone mass is becoming widely accepted (11,14,27). The beneficial effects of exercise on bone mass and mechanical competence can be attributed to bone tissue’s sensitivity to physical forces created in the skeleton during exercise. Bone cells respond to tissue deformation, or its consequences (e.g., fluid flow), by adapting the structure to more adequately withstand future deformations (6). This adaptive process entails adding bone (either with or without prior resorption) to appropriate skeletal surfaces (7,8). However, the type of exercise modulates the anabolic response; high-impact exercises (e.g., volleyball, gymnastics) are more effective than low-impact exercises (e.g., cycling, swimming) in promoting bone gain (2,23,24). Data from animal experiments and mathematical modeling suggest that the osteogenic effects of high-impact exercise in humans are probably related to the greater strain rates associated with those activities (15,16,26). Another important factor governing the anabolic response to exercise is skeletal age. Although exercise during the adult years can retard the natural bone loss associated with aging, a much greater improvement in bone mass (and fracture resistance later in life) is achieved if vigorous exercise is engaged in during the childhood and adolescent years, when peak bone mass can still be affected (10,12,13,17).

Although the effects of exercise on bone health are becoming clear, little is known about how exercise protocols can be optimized to further promote bone mass accumulation and maintenance. A major factor to consider in designing exercise programs aimed at maintaining or improving bone mass is the sensitivity of the resident bone cell populations to mechanical stimuli. Animal loading experiments have demonstrated that bone cells desensitize soon after a loading session is initiated. The osteogenic effects of exercise could therefore reach a saturation point (where the cells are essentially unresponsive to further stimulation), perhaps after 50–100 repetitions of loading (22,26,28). These data indicate that extended exercise sessions are no more beneficial to bone mass than shorter sessions because the maximal osteogenic response is probably achieved within the first few minutes.

In a previous communication, we showed that partitioning a daily mechanical stimulus (360 repetitions of load per day) into smaller loading bouts, separated by recovery periods, enhanced bone formation over that elicited from the same stimulus applied in a single, uninterrupted loading bout (20). Presumably, the bone cells in the single, longer bout had lost sensitivity early in the session, so that load repetitions occurring toward the end of the bout were ignored. By making the loading sessions shorter and providing recovery periods between sessions (during which mechanosensitivity could be restored), bone formation improved by as much as 90%. A follow-up experiment showed that approximately 8 h of load-free recovery restores full mechanosensitivity to previously stimulated bone cells (21). Mechanical loading sessions initiated before full recovery was achieved resulted in bone formation rates that were proportional to the recovery time, indicating that even modest recovery periods can restore some degree of sensitivity.

Although our previous studies have shed light on the dynamics of bone cell mechanosensitivity, they were limited in that the duration of the loading protocol lasted from 1 to 2 wk. In light of strain-feedback models of bone adaptation (6), it was unclear whether the improvement in bone formation using short, separated bouts would be maintained if the loading protocols were implemented over a longer time period. Using a noninvasive loading model that applies well-controlled forces to the rat ulna, we sought to determine whether 4 months of loading using short loading bouts, interspersed with recovery periods, is more beneficial than single, longer daily sessions. We hypothesized that after 16 wk of loading, bone mass and structural properties of ulnae loaded for 90 cycles, 4 times·d−1 would be greater than in ulnae loaded for 360 uninterrupted cycles·d−1.

Back to Top | Article Outline

MATERIALS AND METHODS

Forty-four virgin female Sprague-Dawley (12 wk old) rats were purchased for the experiment from Harlan Sprague-Dawley (Indianapolis, IN). The rats were housed two per cage at Indiana University’s Laboratory Animal Resource Center for 15 wk before the experiment began (acclimation period) and were provided standard rat chow and water ad libitum during the acclimation and experimental periods. Body mass measurements were collected periodically during the acclimation period and 3 times/wk during the experimental (loading) period. Under ether-induced anesthesia, the right ulna of rats in the loading groups was subjected to axially applied compressive loads, using a nonsurgical loading preparation that transmits mechanical force to the ulna through the olecranon and flexed carpus (Fig. 1A) (25). The natural curvature of the ulnar diaphysis translates the axial load into a bending moment in the middiaphysis that produces tension in the lateral cortex and compression in the medial cortex. Force was applied to the ulnae by an open loop, stepper motor-driven spring linkage with an in-line load cell. All procedures performed in this experiment were conducted in AAALAC-approved facilities and were in accordance with ACSM, NIH, and Indiana University Animal Care and Use Committee guidelines.

Figure 1
Figure 1
Image Tools
Back to Top | Article Outline
Experimental design.

Ten days before the start of the loading period, the rats were divided randomly into two loaded groups (N = 13/group) and two control groups (N = 9/group). The right ulnae of animals in the two loaded groups were subjected to 360 load cycles·d−1, 3 d·wk−1 for 16 consecutive weeks. Load was applied as a haversine waveform at a frequency of 2 Hz and peak load magnitude of 17 N, which elicits a compressive strain of approximately 3600 με on the medial surface of the ulnar midshaft (9). The two loaded groups differed from each another only in the timed delivery of the 360 load cycles received throughout each load day. One group was administered all 360 cycles in a single, uninterrupted session (360×1), which lasted 3 min. The other loaded group was administered the 360 cycles in four discrete bouts of 90 cycles/bout (90×4), with 3 h of recovery inserted between each of the brief (45-s long) loading bouts. We have shown previously, using the rat tibia bending model, that the 90×4 schedule enhances bone formation markedly over that produced by the 360×1 schedule after 1 wk of loading (20). All rats were allowed normal cage activity between bouts. The two control groups comprised a baseline control (BLC) group, which was sacrificed on the first loading day, and an age-matched control (AMC) group, which was sacrificed on the same day that the loaded groups were sacrificed (16 wk after baseline sacrifice). Neither control group was subjected to loading or anesthesia. In the loaded groups, the left ulnae were not loaded and served as internal controls for the loaded limb. After sacrifice, the right and left ulnae were dissected free of the articulating bones, cleaned of soft tissues, fixed in 10% neutral buffered formalin for 48 h, then transferred to 70% ethanol for storage.

Back to Top | Article Outline
DXA.

Each right-left ulna pair was scanned side-by-side on the bed of a Hologic QDR-1000 x-ray densitometer (Hologic Inc., Waltham, MA) equipped with Hologic version 6.20C software. The bones were positioned with the lateral surface of the diaphysis facing down and were scanned at 0.127-mm resolution. Upon completion of each scan, mutually exclusive region of interest (ROI) boxes were drawn around the right and left bone, from which bone area (BA; cm2), bone mineral content (BMC; mg), and areal bone mineral density (aBMD; g·cm−2) measurements were collected. Two bones from the study, chosen at random, were scanned 10 times to assess reproducibility. The bone was removed from the scanner bed and repositioned between each repeat scan. From the 10 repeated measures, the coefficient of variation (CV) was calculated. The CVs for BMC and aBMD were 1.5% and 1.0%, respectively.

Back to Top | Article Outline
pQCT.

Each ulna was placed in a plastic tube filled with 70% ethanol and centered in the gantry of a Norland Stratec XCT Research SA+ pQCT (Stratec Electronics, Pforzheim, Germany). Two cross-sectional levels were scanned on each ulna—one at the midshaft and one through the olecranon process, using 0.46 mm collimation (4×105 counts·s−1) and 0.08 mm voxel size (Fig. 1B). The slice through the olecranon was taken 3.5 mm distal to the proximal tip of the bone and included the cortical shell and secondary spongiosa of the proximal metaphysis. For each section, the x-ray source was rotated through 180° of projection (1 block). The scans were imported into BonAlyse version 1.3 software (BonAlyse Ltd., Jyväskyla, Finland) for post hoc pQCT analyses. From the midshaft slices, total cross sectional area (CSA—area within periosteum; mm2), cortical volumetric BMD (vBMD; mg·cm−3), and maximum and minimum second moments of area (IMAX and IMIN; mm4) were calculated in BonAlyse. The second moment of area (I) reflects a structure’s resistance to bending by considering both cross-sectional area and material distribution (geometry). Beams (or long bone shafts) with the material distributed farther from the plane of bending will exhibit greater resistance to bending (I) than beams with material distributed closer to the plane of bending. This geometry-related increase in bending rigidity can occur even with reduced cross sectional area if the material is appropriately distributed. I is calculated by dividing the section into a series of small areas (pixels) and multiplying each area (dA) by its squared distance (y) from the neutral plane. This procedure is integrated over the entire cross section:MATH

Equation U1
Equation U1
Image Tools

This function is repeated about all possible neutral planes; the largest value is returned as IMAX, and the smallest value is returned as IMIN.

Analysis of bone envelopes at the midshaft slice was restricted to cortical bone, because trabecular bone is not normally present in the central diaphysis. From the olecranon slices, CSA and total vBMD were calculated in BonAlyse. Two additional measurements were conducted on the proximal slices to investigate trabecular bone adaptation in the proximal metaphysis. The peel mode in the Stratec software was used to separate cortical from trabecular bone, and vBMD was calculated for each bone envelope separately. Cortical bone was separated from trabecular bone using a density threshold of 900 mg·cm−3. Two bones from the study, chosen at random, were scanned 10 times to assess reproducibility. CVs for the pQCT measurements were as follows: CSA midshaft = 4.4%, cortical vBMD midshaft = 1.8%, IMAX midshaft = 2.0%, IMIN midshaft = 3.8%, CSA proximal = 4.0%, and total vBMD proximal = 1.9%.

Back to Top | Article Outline
Statistical analyses.

Differences between right (loaded limb) versus left (control limb) values for all DXA and pQCT measurements were tested for significance using paired t-tests. Percent differences between right (R) and left (L) limbs were calculated as follows: (R − L)/L·100. One-way analysis of variance (ANOVA) was performed on control limb and percent difference values to detect differences among the four experimental groups. Significant ANOVAs were followed by Fisher’s PLSD post hoc tests to determine significant differences between individual experimental groups. For the t-tests, ANOVA, and post hoc tests, α = 0.05.

Back to Top | Article Outline

RESULTS

Two of the rats in the 360×1 group died toward the end of the experimental period, one from anesthesia-related complications and the other from unknown causes. One of the baseline control animals died during the acclimation period from unknown causes, and one animal from the age-matched control group was excluded from the DXA analysis and from the pQCT analysis of the olecranon because of tissue damage to the proximal ulna during processing. Over the 16-wk loading period, mean body mass increased slightly in each group (6–12%) but exhibited substantial fluctuation, even in the age-matched control group (Fig. 2). The age-matched control group gained significantly more weight than the 90×4 group (Fig. 2, inset), suggesting an effect of multiple ether exposures on body weight.

Figure 2
Figure 2
Image Tools

BMC in the left (control) ulnae was significantly different among groups (P = 0.016). Post hoc tests revealed significant differences between the baseline control group and the remaining three groups only; none of the 16-wk animals were significantly different from one another. Thus, there appears to be an aging effect but no systemic loading effect on BMC in the control limb. Paired t-tests revealed no significant differences between right and left limbs for BMC in either control group, but both loading groups exhibited significantly (P < 0.001) greater BMC in the loaded limb compared with the control limb (Table 1). Although both loaded groups showed significant loading effects, the percent difference between right and left ulnar BMC in the 90×4 group (11.7%) was 70% greater (P = 0.001) than the right versus left difference in the 360×1 group (6.9%;Fig. 3).

Figure 3
Figure 3
Image Tools
Table 1
Table 1
Image Tools

Areal BMD (aBMD) in the control ulna was not significantly different among groups (P = 0.68). Paired t-tests revealed no significant differences between right and left limbs for aBMD in either control group, but both loading groups exhibited significantly (P < 0.001) greater aBMD in the loaded limb when compared with the control limb (Table 1). The percent difference between right and left ulnar aBMD in the 90×4 group (8.6%) was approximately 60% greater (P = 0.012) than the right versus left difference in the 360×1 group (5.4%;Fig. 3).

Peripheral QCT measurements collected from the ulnar midshaft of control (left) limbs yielded significant differences among groups for vBMD and IMAX. Post hoc pairwise comparisons among groups performed on control limb vBMD and IMAX revealed significant differences (P < 0.05) between the baseline control group and each of the remaining three groups. The three groups sacrificed at 16 wk were not significantly different from one another. Paired t-tests showed significantly (P < 0.001) greater CSA, vBMD, IMAX, and IMIN in the loaded arm compared with the control arm in both loaded groups (Table 2). With the exception of IMIN in the baseline control group and IMAX in the age-matched control group, paired t-test P-values were not significant for any of the variables in the two control groups.

Table 2
Table 2
Image Tools

The percent difference between right and left midshaft ulna cross-sectional area was significantly greater in the loaded groups compared with the control groups (Fig. 4). Differences were also detected between loading groups—the 90×4 group exhibited 37% greater (P = 0.012) right versus left difference in CSA than the 360×1 group (Fig. 4). Percent difference (right vs left) for vBMD was significantly greater in the loaded groups compared with the control groups, but no significant differences between the two loaded groups were detected (Fig. 5). Percent difference in IMAX and IMIN was also significantly greater among the loaded groups compared with the control groups, with the exception of the 360×1 versus baseline control post hoc comparison for IMAX (Fig. 6). Between loaded groups, IMIN (but not IMAX) was significantly greater in the 90×4 group (46% greater;P < 0.001) compared with the 360×1 group (Fig. 6).

Figure 4
Figure 4
Image Tools
Figure 5
Figure 5
Image Tools
Figure 6
Figure 6
Image Tools

Measurements at the olecranon of the left ulnae yielded significant differences among groups in total vBMD and cortical vBMD; however, no differences in left limb CSA or trabecular bone vBMD were detected. Post hoc pairwise comparisons among groups were performed on total and cortical vBMD, and revealed significant differences (P < 0.05) between the baseline control group and each of the remaining three groups. The three groups sacrificed at 16 wk were not significantly different from one another. Paired t-tests detected no significant differences between right and left values for any of the olecranon measurements, with the exception of total vBMD in the 90×4 group (Table 2).

Back to Top | Article Outline

DISCUSSION

Our objective was to determine whether the beneficial osteogenic effects of a daily high-impact exercise protocol employing multiple short bouts would be preserved after 4 months of training. We found that ulnae from the 90×4 group had significantly greater BMC, aBMD, and minimum second moment of area at midshaft, compared with ulnae from the 360×1 group. These findings suggest that long-term (several months in duration) exercise protocols targeting bone health might result in greater returns in bone mass and structural properties if the daily exercise is partitioned into shorter, discrete bouts, rather than a single longer bout.

Both IMAX and IMIN were enhanced significantly by loading, but the load-induced increase in IMIN over controls was 5–6 times greater than the load-induced increase in IMAX over controls. The principal axes at the rat ulnar midshaft correspond roughly to the anatomical axes, with the major axis (plane along which IMAX exists) oriented in the cranial–caudal direction and the minor axis (plane along which IMIN exists) oriented in the medial–lateral direction. Previously characterized strain patterns at the midshaft during external loading (and during normal ambulation in vivo) show that bending occurs in the medial–lateral direction (25). Thus, the greatest change in strains during loading was produced on the medial and lateral surfaces of the midshaft, which is where the majority of the new bone formation occurred as a result of loading. The preferential localization of new bone to the medial and lateral surfaces explains why such large increases in IMIN were found in the loaded groups, particularly in the 90×4 group.

Cortical vBMD at midshaft was significantly increased in the two loaded groups, indicating that loading increased mineralization of the tissue. We did not, however, detect a scheduling difference in vBMD between the two loaded groups, which suggests that mineralization was not affected by the timed delivery of load cycles.

The group differences observed in final body mass corresponded to the number of ether exposures during the loading period, a result we have reported previously (20). Despite the lower final body mass in the 90×4 group, bone mass and structural properties of the right ulna were greatest in this group. The differences in final body mass only strengthen our conclusions regarding the osteogenic response to different loading schedules; if whole bone (BMC, aBMD) and midshaft bending moment (IMAX, IMIN) values are standardized by final body mass, the differences between the 90×4 and 360×1 groups become even greater (from 12 to 50% greater than in unstandardized comparisons). Thus, differences in body mass do not appear to confound the results of this experiment.

Loading failed to produce any significant increase in bone density or mass at the olecranon. The 90×4 group exhibited significantly lower total vBMD in the loaded ulna when compared with the contralateral control ulna, but inspection of Table 2 reveals that this result was produced by an abnormally high control limb value rather than a suppressed value in the loaded bone. The lack of a positive-loading effect at the olecranon might be attributable to the small strains produced at that location during loading. Using a mean cortical bone cross sectional area of 4.2 mm2 collected from the proximal pQCT scans (data not shown) and a previously calculated elastic modulus for rat cortical bone of 29.4 GPa (1), we estimate that strains at the olecranon during peak (17 N) loads reached only 140 με. Considering the much larger strains occurring at the midshaft during peak loads (∼3600 με) (9), it appears possible that strain values at the olecranon were not great enough to exceed the threshold necessary to elicit an osteogenic response.

The Centers for Disease Control and the American College of Sports Medicine have made recommendations for all adults to “accumulate 30 minutes or more of moderate-intensity physical activity on most, preferably all, days of the week”(18). These guidelines were developed to promote exercise among the sedentary population, with the goal of improving general health and lowering risks for many diseases, including heart disease, osteoporosis, cancer, hypertension, and diabetes mellitus (among others). The temporal manner in which the 30 min·d−1 of exercise should be “accumulated” is not yet clear, but it may depend on the physiologic system being targeted for improvement. DeBusk et al. (4) showed that maximal oxygen uptake (V̇O2max) increased significantly more in men who were put on a daily exercise program involving a single, 30-min session each day, when compared with men who were put on a program of similar intensity involving three 10-min sessions each day. Conversely, Ebisu (5) found that high-density lipoprotein cholesterol levels increased significantly in men who ran three times per day, compared with men who ran the same total distance each day but did so in a single bout. Our data suggest that short periods of physical activity, conducted several times each day, might improve bone mass over that achieved from a single, sustained period of daily physical activity.

These data should be considered in light of several limitations of the experiment. We only tested one multiple-bout exercise schedule (90×4). Although we have shown previously in short-term experiments (1 wk of loading) that the osteogenic response to loading varies according to the number of bouts per day (20), it is unclear whether a different multi-bout schedule (e.g., 180×2 or 60×6) would be more or less beneficial than the 90×4 schedule after 4 months. Second, the loads used in this experiment elicited strains that were in excess of those measured in humans during vigorous exercises (3). It is unclear whether proportional benefits would occur at lower strains. Finally, we did find significant right versus left differences in IMAX in the age-matched control group and in IMIN for the baseline control group. In both of these comparisons, right ulna values were significantly lower than left ulna values despite the fact that these animals were not loaded or handled beyond measuring body mass. These two results are difficult to explain. However, in light of the fact that the remaining midshaft and whole-bone measurements showed no significant side-to-side differences in the control groups, it is unlikely that these two observations suggest lateral dominance (left-handedness) in the rats used.

In conclusion, when 360 load repetitions are administered to the rat ulna 3 times·wk−1 for 16 wk, the anabolic response is much greater if the repetitions are divided into four smaller bouts of 90 repetitions/bout, separated by 3-h recovery periods, than if they are applied in a single, uninterrupted bout. These findings support other experimental evidence showing that bone cell mechanosensitivity declines quickly after initiation of a loading bout and suggest that by scheduling bone loading (exercise) sessions during times when the cells are more sensitive to mechanical stimuli, the osteogenic response can be improved. These concepts, applied to human exercise programs, hold potential for improving peak bone mass in the growing skeleton and/or preventing excessive bone loss in the aging skeleton.

We thank J. Ratliff and F. Peacock for technical assistance. This work was supported by NIH grants AR43730 and T32, AR07581.

Address for correspondence: Alexander G. Robling, Ph.D., Department of Anatomy & Cell Biology, Indiana University School of Medicine, 635 Barnhill Dr., MS 5045, Indianapolis, IN 46202; E-mail: arobling@anatomy.iupui.edu.

Back to Top | Article Outline

REFERENCES

1. Akhter, M. P., D. M. Raab, C. H. Turner, D. B. Kimmel, and R. R. Recker. Characterization of in vivo strain in the rat tibia during external application of a four-point bending load. J. Biomech. 25: 1241–1246, 1992.

2. Bassey, E. J., and S. J. Ramsdale. Increase in femoral bone density in young women following high-impact exercise. Osteoporos. Int. 4: 72–75, 1994.

3. Burr, D. B., C. Milgrom, D. Fyhrie, et al. In vivo measurement of human tibial strains during vigorous activity. Bone 18: 405–410, 1996.

4. Debusk, R. F., U. Stenestrand, M. Sheehan, and W. L. Haskell. Training effects of long versus short bouts of exercise in healthy subjects. Am. J. Cardiol 65: 1010–1013, 1990.

5. Ebisu, T. Splitting the distance of endurance running: on cardiovascular endurance and blood lipids. Jpn. J. Phys. Educ. 30: 37–43, 1985.

6. Frost, H. M. Bone “mass” and the “mechanostat”: a proposal. Anat. Rec. 219: 1–9, 1987.

7. Frost, H. M. Skeletal structural adaptations to mechanical usage (SATMU): 1. Redefining Wolff’s law: the bone modeling problem. Anat. Rec. 226: 403–413, 1990.

8. Frost, H. M. Skeletal structural adaptations to mechanical usage (SATMU): 2. Redefining Wolff’s law: the remodeling problem. Anat. Rec. 226: 414–422, 1990.

9. Hsieh, Y. F., T. Wang, and C. H. Turner. Viscoelastic response of the rat loading model: implications for studies of strain-adaptive bone formation. Bone 25: 379–382, 1999.

10. Kannus, P., H. Haapasalo, M. Sankelo, et al. Effect of starting age of physical activity on bone mass in the dominant arm of tennis and squash players. Ann. Intern. Med. 123: 27–31, 1995.

11. Kannus, P., H. Sievanen, and I. Vuori. Physical loading, exercise, and bone. Bone 18: 1S–3S, 1996.

12. Khan, K., H. A. McKay, H. Haapasalo, et al. Does childhood and adolescence provide a unique opportunity for exercise to strengthen the skeleton? J. Sci. Med. Sport 3: 150–164, 2000.

13. Kontulainen, S., P. Kannus, H. Haapasalo, et al. Good maintenance of exercise-induced bone gain with decreased training of female tennis and squash players: a prospective 5-year follow-up study of young and old starters and controls. J. Bone Miner. Res. 16: 195–201, 2001.

14. Marcus, R. Exercise: moving in the right direction. J. Bone Miner. Res. 13: 1793–1796, 1998.

15. Milgrom, C., A. Finestone, A. Simkin, et al. In-vivo strain measurements to evaluate the strengthening potential of exercises on the tibial bone. J. Bone Joint Surg. Br. 82: 591–594, 2000.

16. Mosley, J. R., and L. E. Lanyon. Strain rate as a controlling influence on adaptive modeling in response to dynamic loading of the ulna in growing male rats. Bone 23: 313–318, 1998.

17. Nelson, D. A., and M. L. Bouxsein. Exercise maintains bone mass, but do people maintain exercise? J. Bone Miner. Res. 16: 202–205, 2001.

18. Pate, R. R., M. Pratt, S. N. Blair, et al. Physical activity and public health: a recommendation from the Centers for Disease Control and Prevention and the American College of Sports Medicine. JAMA 273: 402–407, 1995.

19. Robling, A. G., K. M. Duijvelaar, J. V. Geevers, N. Ohashi, and C. H. Turner. Modulation of longitudinal and appositional bone growth in the rat ulna by applied static and dynamic force. Bone 29: 105–113, 2001.

20. Robling, A. G., D. B. Burr, and C. H. Turner. Partitioning a daily mechanical stimulus into discrete loading bouts improves the osteogenic response to loading. J. Bone Miner. Res. 15: 1596–1602, 2000.

21. Robling, A. G., D. B. Burr, and C. H. Turner. Recovery periods restore mechanosensitivity to dynamically loaded bone. J. Exp. Biol. 204: 3389–3399, 2001.

22. Rubin, C. T., and L. E. Lanyon. Regulation of bone formation by applied dynamic loads. J. Bone Joint Surg. [Am.] 66: 397–402, 1984.

23. Taaffe, D. R., T. L. Robinson, C. M. Snow, and R. Marcus. High-impact exercise promotes bone gain in well-trained female athletes. J. Bone Miner. Res. 12: 255–260, 1997.

24. Taaffe, D. R., C. Snow-Harter, D. A. Connolly, T. L. Robinson, M. D. Brown, and R. Marcus. Differential effects of swimming versus weight-bearing activity on bone mineral status of eumenorrheic athletes. J. Bone Miner. Res. 10: 586–593, 1995.

25. Torrance, A. G., J. R. Mosley, R. F. Suswillo, and L. E. Lanyon. Noninvasive loading of the rat ulna in vivo induces a strain-related modeling response uncomplicated by trauma or periosteal pressure. Calcif. Tissue Int. 54: 241–247, 1994.

26. Turner, C. H. Three rules for bone adaptation to mechanical stimuli. Bone 23: 399–407, 1998.

27. Turner, C. H. Exercising the skeleton: beneficial effects of mechanical loading on bone structure. The Endocrinologist 10: 164–169, 2000.

28. Umemura, Y., T. Ishiko, T. Yamauchi, M. Kurono, and S. Mashiko. Five jumps per day increase bone mass and breaking force in rats. J. Bone Miner. Res. 12: 1480–1485, 1997.

Cited By:

This article has been cited 72 time(s).

Physiological Reviews
Nuclear Receptors in Bone Physiology and Diseases
Imai, Y; Youn, MY; Inoue, K; Takada, I; Kouzmenko, A; Kato, S
Physiological Reviews, 93(2): 481-523.
10.1152/physrev.00008.2012
CrossRef
Sports Medicine
Effects of Weight-Bearing Exercise on Bone Health in Girls: A Meta-Analysis
Ishikawa, S; Kim, Y; Kang, M; Morgan, DW
Sports Medicine, 43(9): 875-892.
10.1007/s40279-013-0060-y
CrossRef
Hip International
High-frequency and low-magnitude whole body vibration with rest days is more effective in improving skeletal micro-morphology and biomechanical properties in ovariectomised rodents
Ma, RS; Zhu, D; Gong, H; Gu, GS; Huang, X; Gao, JZ; Zhang, XZ
Hip International, 22(2): 218-226.
10.5301/HIP.2012.9033
CrossRef
Journal of Biological Chemistry
The Wnt co-receptor LRP5 is essential for skeletal mechanotransduction but not for the anabolic bone response to parathyroid hormone treatment
Sawakami, K; Robling, AG; Ai, MR; Pitner, ND; Liu, DW; Warden, SJ; Li, JL; Maye, P; Rowe, DW; Duncan, RL; Warman, ML; Turner, CH
Journal of Biological Chemistry, 281(): 23698-23711.
10.1074/jbc.M601000200
CrossRef
Bone
The effect of weight loading and subsequent release from loading on the postnatal skeleton
Reich, A; Sharir, A; Zelzer, E; Hacker, L; Monsonego-Ornan, E; Shahar, R
Bone, 43(4): 766-774.
10.1016/j.bone.2008.06.004
CrossRef
Current Pharmaceutical Design
Exercise as an anabolic stimulus for bone
Turner, CH; Robling, AG
Current Pharmaceutical Design, 10(): 2629-2641.

Journal of Biomechanics
Cellular accommodation and the response of bone to mechanical loading
Schriefer, JL; Warden, SJ; Saxon, LK; Robling, AG; Turner, CH
Journal of Biomechanics, 38(9): 1838-1845.
10.1016/j.jbiomech.2004.08.017
CrossRef
Applied Physiology Nutrition and Metabolism-Physiologie Appliquee Nutrition Et Metabolisme
Can body weight supported treadmill training increase bone mass and reverse muscle atrophy in individuals with chronic incomplete spinal cord injury?
Giangregorio, LM; Webber, CE; Phillips, SM; Hicks, AL; Craven, BC; Bugaresti, JM; McCartney, N
Applied Physiology Nutrition and Metabolism-Physiologie Appliquee Nutrition Et Metabolisme, 31(3): 283-291.
10.1139/H05-036
CrossRef
International Journal of Sports Medicine
Effect of exercise, body composition, and nutritional intake on bone parameters in male elite rock climbers
Kemmler, W; Roloff, I; Baumann, H; Schoffl, V; Weineck, J; Kalender, W; Engelke, K
International Journal of Sports Medicine, 27(8): 653-659.
10.1055/s-2005-872828
CrossRef
Journal of Bone and Mineral Research
Tower climbing exercise started 3 months after ovariectomy recovers bone strength of the femur and lumbar vertebrae in aged osteopenic rats
Notomi, T; Okimoto, N; Okazaki, Y; Nakamura, T; Suzuki, M
Journal of Bone and Mineral Research, 18(1): 140-149.

Journal of Rehabilitation Research and Development
Whole-body vibration as potential intervention for people with low bone mineral density and osteoporosis: A review
de Zepetnek, JOT; Giangregorio, LM; Craven, BC
Journal of Rehabilitation Research and Development, 46(4): 529-542.
10.1682/JRRD.2008.09.0136
CrossRef
Journal of Cellular Physiology
Long-term loading inhibits ERK1/2 phosphorylation and increases FGFR3 expression in MC3T3-E1 osteoblast cells
Jackson, RA; Kumarasuriyar, A; Nurcombe, V; Cool, SM
Journal of Cellular Physiology, 209(3): 894-904.
10.1002/jcp.20779
CrossRef
Calcified Tissue International
Additional weight bearing during exercise and estrogen in the rat: The effect on bone mass, turnover, and structure
Tromp, AM; Bravenboer, N; Tanck, E; Oostlander, A; Holzmann, PJ; Kostense, PJ; Roos, JC; Burger, EH; Huiskes, R; Lips, P
Calcified Tissue International, 79(6): 404-415.
10.1007/s00223-006-0045-z
CrossRef
Biomechanics and Modeling in Mechanobiology
Mechanically induced intracellular calcium waves in osteoblasts demonstrate calcium fingerprints in bone cell mechanotransduction
Godin, LM; Suzuki, S; Jacobs, CR; Donahue, HJ; Donahue, SW
Biomechanics and Modeling in Mechanobiology, 6(6): 391-398.
10.1007/s10237-006-0059-5
CrossRef
Osteoporosis International
Anterior-posterior bending strength at the tibial shaft increases with physical activity in boys: evidence for non-uniform geometric adaptation
Macdonald, HM; Cooper, DML; Mckay, HA
Osteoporosis International, 20(1): 61-70.
10.1007/s00198-008-0636-9
CrossRef
Journal of Womens Health
Habitual Site-Specific Upper Extremity Loading is Associated with Increased Bone Mineral of the Ultradistal Radius in Young Women
Bareither, ML; Grabiner, MD; Troy, KL
Journal of Womens Health, 17(): 1577-1581.
10.1089/jwh.2008.0888
CrossRef
Clinical Oral Implants Research
Bone reactions to controlled loading of endosseous implants: a pilot study
Wiskott, HWA; Cugnoni, J; Scherrer, SS; Ammann, P; Botsis, J; Belser, UC
Clinical Oral Implants Research, 19(): 1093-1102.
10.1111/j.1600-0501.2008.01548.x
CrossRef
Osteoporosis International
Minimum level of jumping exercise required to maintain exercise-induced bone gains in female rats
Ooi, FK; Singh, R; Singh, HJ; Umemura, Y
Osteoporosis International, 20(6): 963-972.
10.1007/s00198-008-0760-6
CrossRef
Calcified Tissue International
Isokinetic Resistance Training Increases Tibial Bending Stiffness in Young Women
Miller, LE; Nickols-Richardson, SM; Wootten, DF; Ramp, WK; Steele, CR; Cotton, JR; Carneal, JP; Herbert, WG
Calcified Tissue International, 84(6): 446-452.
10.1007/s00223-009-9247-5
CrossRef
Journal of Bone and Mineral Research
Improved bone structure and strength after long-term mechanical loading is greatest if loading is separated into short bouts
Robling, AG; Hinant, FM; Burr, DB; Turner, CH
Journal of Bone and Mineral Research, 17(8): 1545-1554.

Spinal Cord
Body weight supported treadmill training in acute spinal cord injury: impact on muscle and bone
Giangregorio, LM; Hicks, AL; Webber, CE; Phillips, SM; Craven, BC; Bugaresti, JM; McCartney, N
Spinal Cord, 43(): 649-657.
10.1038/sj.sc.3101774
CrossRef
Pediatric Exercise Science
What does the animal model teach us about the effects of physical activity on growing bone?
Forwood, MR
Pediatric Exercise Science, 18(3): 282-289.

Journal of Experimental Biology
The effect of endurance exercise on the morphology of muscle attachment sites
Zumwalt, A
Journal of Experimental Biology, 209(3): 444-454.
10.1242/jeb.02028
CrossRef
Bone
High impact exercise is more beneficial than dietary calcium for building bone strength in the growing rat skeleton
Welch, JM; Tumer, CH; Devareddy, L; Arjmandi, BH; Weaver, CM
Bone, 42(4): 660-668.
10.1016/j.bone.2007.12.220
CrossRef
Journal of Bone and Mineral Research
Winning the battle against childhood physical inactivity: The key to bone strength?
McKay, H; Smith, E
Journal of Bone and Mineral Research, 23(7): 980-985.
10.1359/JBMR.080306
CrossRef
Osteoporosis International
The BPAQ: a bone-specific physical activity assessment instrument
Weeks, BK; Beck, BR
Osteoporosis International, 19(): 1567-1577.
10.1007/s00198-008-0606-2
CrossRef
Journal of Biomechanics
Adaptation of cellular mechanical behavior to mechanical loading for osteoblastic cells
Jaasma, MJ; Jackson, WM; Tang, RY; Keaveny, TM
Journal of Biomechanics, 40(9): 1938-1945.
10.1016/j.jbiomech.2006.09.010
CrossRef
Biomechanics and Modeling in Mechanobiology
Continuum remodeling revisited - Deformation rate driven functional adaptation using a hypoelastic constitutive law
Negus, CH; Impelluso, TJ
Biomechanics and Modeling in Mechanobiology, 6(4): 211-226.
10.1007/s10237-006-0050-1
CrossRef
Scandinavian Journal of Medicine & Science in Sports
Recreational football training decreases risk factors for bone fractures in untrained premenopausal women
Helge, EW; Aagaard, P; Jakobsen, MD; Sundstrup, E; Randers, MB; Karlsson, MK; Krustrup, P
Scandinavian Journal of Medicine & Science in Sports, 20(): 31-39.
10.1111/j.1600-0838.2010.01107.x
CrossRef
Journal of Applied Physiology
Effects of intervals between jumps or bouts on osteogenic response to loading
Umemura, Y; Sogo, N; Honda, A
Journal of Applied Physiology, 93(4): 1345-1348.
10.1152/japplphysiol.00358.2002
CrossRef
Journal of Bone and Mineral Research
Ten-year longitudinal relationship between physical activity and lumbar bone mass in (young) adults
Bakker, I; Twisk, JW; Van Mechelen, W; Roos, JC; Kemper, HC
Journal of Bone and Mineral Research, 18(2): 325-332.

Journal of Applied Physiology
Rest insertion combined with high-frequency loading enhances osteogenesis
LaMothe, JM; Zernicke, RF
Journal of Applied Physiology, 96(5): 1788-1793.
10.1152/japplphysiol.01145.2003
CrossRef
Journal of Cystic Fibrosis
Exercise during childhood and adolescence: A prophylaxis against cystic fibrosis-related low bone mineral density? Exercise for bone health in children with cystic fibrosis
Hind, K; Truscott, JG; Conway, SP
Journal of Cystic Fibrosis, 7(4): 270-276.
10.1016/j.jcf.2008.02.001
CrossRef
Critical Reviews in Eukaryotic Gene Expression
Mechanical Signaling for Bone Modeling and Remodeling
Robling, AG; Turner, CH
Critical Reviews in Eukaryotic Gene Expression, 19(4): 319-338.

Journal of Applied Physiology
Adaptations to free-fall impact are different in the shafts and bone ends of rat forelimbs
Welch, JM; Weaver, CM; Turner, CH
Journal of Applied Physiology, 97(5): 1859-1865.
10.1152/japplphysiol.00438.2004
CrossRef
Sports Medicine
Physical activity in the prevention and amelioration of osteoporosis in women - Interaction of mechanical, hormonal and dietary factors
Borer, KT
Sports Medicine, 35(9): 779-830.

Bone
Isokinetic training increases ulnar bending stiffness and bone mineral in young women
Miller, LE; Wootten, DF; Nickols-Richardson, SM; Ramp, WK; Steele, CR; Cotton, JR; Carneal, JP; Herbert, WG
Bone, 41(4): 685-689.
10.1016/j.bone.2007.07.004
CrossRef
Acta Paediatrica
A 2-year school-based exercise programme in pre-pubertal boys induces skeletal benefits in lumbar spine
Alwis, G; Linden, C; Ahlborg, HG; Dencker, M; Gardsell, P; Karlsson, MK
Acta Paediatrica, 97(): 1564-1571.
10.1111/j.1651-2227.2008.00960.x
CrossRef
Journal of Orthopaedic Research
Skeletal Muscle Contractions Uncoupled from Gravitational Loading Directly Increase Cortical Bone Blood Flow Rates In Vivo
Caulkins, C; Ebramzadeh, E; Winet, H
Journal of Orthopaedic Research, 27(5): 651-656.
10.1002/jor.20780
CrossRef
Journal of Sports Medicine and Physical Fitness
Bone mineral density and sport: effect of physical activity
Pigozzi, F; Rizzo, M; Giombini, A; Parisi, A; Fagnani, F; Borrione, P
Journal of Sports Medicine and Physical Fitness, 49(2): 177-183.

Journal of Morphology
Experimental evolution and phenotypic plasticity of hindlimb bones in high-activity house mice
Kelly, SA; Czech, PP; Wight, JT; Blank, KM; Garland, T
Journal of Morphology, 267(3): 360-374.
10.1002/jmor.10407
CrossRef
Bone
Bone mineral density in female high school athletes: Interactions of menstrual function and type of mechanical loading
Nichols, JF; Rauh, MJ; Barrack, MT; Barkai, HS
Bone, 41(3): 371-377.
10.1016/j.bone.2007.05.003
CrossRef
Clinical Orthopaedics and Related Research
Pause insertions during cyclic in vivo loading affect bone healing
Gardner, MJ; Ricciardi, BF; Wright, TM; Bostrom, MP; van der Meulen, MCH
Clinical Orthopaedics and Related Research, 466(5): 1232-1238.
10.1007/s11999-008-0155-1
CrossRef
Journal of Bone and Mineral Metabolism
High-impact exercise frequency per week or day for osteogenic response in rats
Umemura, Y; Nagasawa, S; Honda, A; Singh, R
Journal of Bone and Mineral Metabolism, 26(5): 456-460.
10.1007/s00774-007-0848-7
CrossRef
Integrative and Comparative Biology
Selective breeding as a tool to probe skeletal response to high voluntary locomotor activity in mice
Middleton, KM; Kelly, SA; Garland, T
Integrative and Comparative Biology, 48(3): 394-410.
10.1093/icb/icn057
CrossRef
In Vitro Cellular & Developmental Biology-Animal
Osteoblasts subjected to spaceflight and simulated space shuttle launch conditions
Kacena, MA; Todd, P; Landis, WJ
In Vitro Cellular & Developmental Biology-Animal, 39(): 454-459.

Annals of Biomedical Engineering
Inbred Strain-Specific Effects of Exercise in Wild Type and Biglycan Deficient Mice
Wallace, JM; Golcuk, K; Morris, MD; Kohn, DH
Annals of Biomedical Engineering, 38(4): 1607-1617.
10.1007/s10439-009-9881-0
CrossRef
Bone
Degradation of bone structural properties by accumulation and coalescence of microcracks
Danova, NA; Colopy, SA; Radtke, CL; Kalscheur, VL; Markel, MD; Vanderby, R; McCabe, RP; Escarcega, AJ; Muir, P
Bone, 33(2): 197-205.
10.1016/S8756-3282(03)00155-8
CrossRef
Bone
Low-dose estrogen treatment suppresses periosteal bone formation in response to mechanical loading
Saxon, LK; Turner, CH
Bone, 39(6): 1261-1267.
10.1016/j.bone.2006.06.030
CrossRef
Japanese Journal of Physical Fitness and Sports Medicine
Effect of high-impact training at different frequencies on osteogenic response in rats
Sogo, N; Honda, A; Nagasawa, S; Umemura, Y
Japanese Journal of Physical Fitness and Sports Medicine, 56(2): 233-240.

Deutsche Zeitschrift Fur Sportmedizin
Exercise recommendations for an increase of bone strength based on animal models and studies with athletes
Kemmler, W; von Stengel, S; Weineck, J; Engelke, K
Deutsche Zeitschrift Fur Sportmedizin, 54(): 306-316.

American Journal of Clinical Nutrition
Dose response of bone mass to dietary arachidonic acid in piglets fed cow milk-based formula
Blanaru, JL; Kohut, JR; Fitzpatrick-Wong, SC; Weiler, HA
American Journal of Clinical Nutrition, 79(1): 139-147.

Tissue Engineering Part A
Osteoblast Response to Rest Periods During Bioreactor Culture of Collagen-Glycosaminoglycan Scaffolds
Plunkett, NA; Partap, S; O'Brien, FJ
Tissue Engineering Part A, 16(3): 943-951.
10.1089/ten.tea.2009.0345
CrossRef
Journal of Biomechanics
Effects of broad frequency vibration on cultured osteoblasts
Tanaka, SM; Li, JL; Duncan, RL; Yokota, H; Burr, DB; Turner, CH
Journal of Biomechanics, 36(1): 73-80.
PII S0021-9290(02)00245-2
CrossRef
Journal of Spinal Cord Medicine
Bone loss and muscle atrophy in spinal cord injury: Epidemioloqy, fracture prediction, and rehabilitation strategies
Giangregorio, L; McCartney, N
Journal of Spinal Cord Medicine, 29(5): 489-500.

Experimental Gerontology
Effects of a progressive loading exercise program on the bone and skeletal muscle properties of female osteopenic rats
Renno, ACM; Gomes, ARS; Nascimento, RB; Salvini, T; Parizoto, N
Experimental Gerontology, 42(6): 517-522.
10.1016/j.exger.2006.11.014
CrossRef
Tissue Engineering Part A
Mechanical stimulation of osteoblasts using steady and dynamic fluid flow
Jaasma, MJ; O'Brien, FJ
Tissue Engineering Part A, 14(7): 1213-1223.
10.1089/ten.tea.2007.0321
CrossRef
Osteoporosis International
Sarcopenia: etiology, clinical consequences, intervention, and assessment
Lang, T; Streeper, T; Cawthon, P; Baldwin, K; Taaffe, DR; Harris, TB
Osteoporosis International, 21(4): 543-559.
10.1007/s00198-009-1059-y
CrossRef
Nutrition
Planning strategies for development of effective exercise and nutrition countermeasures for long-duration space flight
Convertino, VA
Nutrition, 18(): 880-888.
PII S0899-9007(02)00939-5
CrossRef
Journal of Applied Physiology
High-impact exercise strengthens bone in osteopenic ovariectomized rats with the same outcome as Sham rats
Honda, A; Sogo, N; Nagasawa, S; Shimizu, T; Umemura, Y
Journal of Applied Physiology, 95(3): 1032-1037.
10.1152/japplphysiol.00781.2002
CrossRef
Journal of Bone and Mineral Metabolism
Mechanisms by which exercise improves bone strength
Turner, CH; Robling, AG
Journal of Bone and Mineral Metabolism, 23(): 16-22.

Bone
Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia
Fritton, JC; Myers, ER; Wright, TM; van der Meulen, MCH
Bone, 36(6): 1030-1038.
10.1016/j.bone.2005.02.013
CrossRef
Tissue Engineering
Mechanical stimulation of MC3T3 osteoblastic cells in a bone tissue-engineering bioreactor enhances prostaglandin E-2 release
Vance, J; Galley, S; Liu, DF; Donahue, SW
Tissue Engineering, 11(): 1832-1839.

International Journal of Biochemistry & Cell Biology
Current perspectives on NMDA-type glutamate signalling in bone
Spencer, GJ; McGrath, CJ; Genever, PG
International Journal of Biochemistry & Cell Biology, 39(6): 1089-1104.
10.1016/j.biocel.2006.11.002
CrossRef
British Journal of Sports Medicine
Regional bone mineral density in male athletes: a comparison of soccer players, runners and controls
Fredericson, M; Chew, K; Ngo, J; Cleek, T; Kiratli, J; Cobb, K
British Journal of Sports Medicine, 41(): 664-668.
10.1136/bjsm.2006.030783
CrossRef
Journal of Applied Physiology
Physical activity and bone development during childhood: insights from animal models
Forwood, MR
Journal of Applied Physiology, 105(1): 334-341.
10.1152/japplphysiol.00040.2008
CrossRef
Journal of Bone and Mineral Research
Climbing exercise increases bone mass and trabecular bone turnover through transient regulation of marrow osteogenic and osteoclastogenic potentials in mice
Mori, T; Okimoto, N; Sakai, A; Okazaki, Y; Nakura, N; Notomi, T; Nakamura, T
Journal of Bone and Mineral Research, 18(): 2002-2009.

Bone
Mechanosensitivity of the rat skeleton decreases after a long period of loading, but is improved with time off
Saxon, LK; Robling, AG; Alam, I; Turner, CH
Bone, 36(3): 454-464.
10.1016/j.bone.2004.12.001
CrossRef
Journal of Biomechanics
Strain distribution in an elastic substrate vibrated in a bioreactor for vocal fold tissue engineering
Titze, IR; Broadhead, K; Tresco, P; Gray, S
Journal of Biomechanics, 38(): 2406-2414.
10.1016/j.jbiomech.2004.10.011
CrossRef
Journal of Rehabilitation Research and Development
Muscle and bone plasticity after spinal cord injury: Review of adaptations to disuse and to electrical muscle stimulation
Dudley-Javoroski, S; Shields, RK
Journal of Rehabilitation Research and Development, 45(2): 283-296.
10.1682/JRRD.2007.02.0031
CrossRef
Clinical Journal of Sport Medicine
Effects of Ball Sports on Future Risk of Stress Fracture in Runners
Fredericson, M; Ngo, J; Cobb, K
Clinical Journal of Sport Medicine, 15(3): 136-141.
10.1097/01.jsm.0000165489.68997.60
PDF (189) | CrossRef
Topics in Geriatric Rehabilitation
Cellular Control of Bone Response to Physical Activity
Smith, EL; Clark, WD
Topics in Geriatric Rehabilitation, 21(1): 77-87.

PDF (112)
Back to Top | Article Outline
Keywords:

MECHANICAL LOADING; BONE ADAPTATION; RECOVERY; EXERCISE; OSTEOPOROSIS; BMD

© 2002 Lippincott Williams & Wilkins, Inc.

Login

Article Tools

Images

Share

Search for Similar Articles
You may search for similar articles that contain these same keywords or you may modify the keyword list to augment your search.

Connect With Us