Table 1.
Experimental conditions for in vivo loading models
| Animal | Age and gender | Limb | F | Peak force | Cycles | Durations | Brief summary | Ref. |
|---|---|---|---|---|---|---|---|---|
| Ulna loading | ||||||||
| Mice | 16 weeks, male and female | Ulna | 2 Hz | 1.0, 1.2, 1.4, 1.6, 1.8 N | 60 per day | 3 days | Both BV/TV and BFR/BS were lower in Lrp5-KO femora than in their control femora. | 157 |
| Mice | 16 weeks, female | Ulna | 2 Hz | 1.90–2.5 N | 120 per day | 3 days, 16 days | Loading induced the strain-dependent increase in bone formation in WT mice, resulting from increases in both mineralizing surface (MS/BS) and mineral apposition rate (MAR). | 30 |
| Mice | 17 weeks, male and female | Ulna | 4 Hz | 3.0 and 4.3 N | 10 min (strain rate of 0.1 sec) | 5 days per week for 2 weeks | Loading to peak strains of 2 000 mu epsilon stimulated lamellar periosteal bone formation, but no response endosteally. Loading to peak strains of 3 000 mu epsilon induced a mixed woven/lamellar periosteal response and lamellar endosteal bone formation. | 33 |
| Mice | 17 weeks, n/a | Ulna | 4 Hz | 2 N | 2 400 per day | 10 days | After loading, the increase of cortical bone thickness was detected in the ulna of both Frzb-KO and control mice. | 207 |
| Mice | 18 weeks, male | Ulna | 2 Hz | 2.7 N | 360 per day | 2 days | Bone-formation rate are in parallel with strain loading intensity; reduced sclerostin expression in osteocytes, particularly in high strain region/midshaft; reduced Sost, Dkk1 mRNA in loading ulnar. | 25 |
| Rats | 9 weeks, male | Ulna | 2 Hz | n/a | 1 200 per day | 4–8 days and 11–15 days | Approximately 90% of the strain produced by axial loading occurs as a result of medial-to-lateral bending, with the remainder due to axial compression. | 208 |
| Rats | 9 weeks, male | Ulna | 2 Hz | n/a | 1 200 per day | 1–5 and 8–12 days | Least squares regression analysis demonstrated a highly significant linear relationship between the magnitude of the applied load and the degree to which longitudinal growth was reduced. | 209 |
| Rats | 27 weeks, female | Ulna | 2 Hz | 17 N | 360 per day | 3 days per week, for 16 weeks | The loaded ulnas exhibited 5.4% and 8.6% greater BMD than the control ulnas in the 360 × 1 and 90 × 4 groups, respectively. BMC was increased by 6.9% and 11.7% in the loaded ulnas of the 360 × 1 and 90 × 4 groups, respectively. | 29 |
| Rats | 17 weeks, female | Ulna | 4 Hz | 3.0 and 4.3 N | 10 min | 5 days per week for 2 weeks | The loading-induced periosteal response increased cortical bone area by 21% ± 4% compared with 0.03% ± 0.02% in controls. | 33 |
| Rats | 20 weeks, female | Ulna | 4 Hz | 20 N | One single stopping point | n/a | Fatigue loading and microdamage formation: Increased TURNL+/Bax+ cells around microdamage, Increased Bcl-2+ cells 1–2 mm away from microdamage. | 175 |
| Rats | 24 weeks, female | Ulna | 2 Hz | 17 N | 360 per day | 2 days | Sost transcripts and sclerostin protein levels were dramatically reduced by ulnar loading. | 25 |
| Tibia loading | ||||||||
| Mice | 10 weeks, male and female | Tibia | 4 Hz | 11.5 ± 0.3 and 2.3 ± 0.3 N | 1 200 per day | 5 days per week, for 2 weeks | Cancellous BV/TV increased 73% in the loaded tibias relative to control tibias. Mean Tb.Th increased (+75%) while Tb.Sp decreased (−19%). Increased tBMD (+18%) contributed to greater bone mass in the loaded tibias following 2 weeks of compression. | 35 |
| Mice | 10 weeks, male | Tibia | n/a | 3 N | 1 200 per day | 5 days per week, for 2 or 6 weeks | The mineral content in both cortical and cancellous bones was enhanced after 6 weeks of loading. Greater responses were found in the cortico-cancellous proximal metaphysis (14%) than the cortical midshaft (2%); bone volume fraction and average trabecular thickness of cancellous bone in the proximal tibia increased after 6 weeks by 15% and 12%, respectively. | 34 |
| Mice | 12, 14 weeks, male | Tibia | 0.1 Hz | 12 N | 40 per day | 3 days per week, for 2 weeks | At the periosteum, loading increased the BFR 15.5-fold and the mineralization perimeter (MPm/BPm) 8.5-fold in control mice. | 210 |
| Mice | 16 weeks, n/a | Tibia | 2 Hz | 9.3 ± 0.9 N | 60 per day | 5 days per week, for 2 weeks | Parameters of new bone formation (i.e., MAR, BFR, and MS) were significantly higher in WT than in cKO tibias after the 2-week loading regimen, with Het mice falling somewhat in between the other two groups. | 98 |
| Mice | 16 weeks, n/a | Tibia | 2 Hz | 9.3 ± 0.9 N | 36 per day | 6 days per week, for 2 weeks | The bone response to external loading is greater in LBD mice than in HBD mice. The high bone density of C3H/HeJ (HBD) mice is related to breed-specific factors other than the response to loading. | 211 |
| Mice | 19 weeks, female | Tibia | 10 Hz | 13.5 N | 40 per day | n/a | Different region of loaded tibiae responded to loading with different loading-related increases of new bone formation. Among all regions, region-III reached a 75-fold increase. Moreover, the magnitude of loading-related decrease in the percentage of sclerostin-positive osteocytes mirrored the amount of loading-related osteogenesis. | 212 |
| Mice | 13–19 weeks female | Tibia and ulnae | 10 Hz | 12.0 N for tibia and 2.5 N for ulna | 40 per day | 10-s intervals between each cycle, for 2 weeks | In trabecular bone of the proximal tibiae, 2 weeks of mechanical loading sufficient by itself to stimulate an osteogenic response, was associated with a 18.6% increase in percent bone volume in the primary spongiosa, a 31.9% increase in percent bone volume in the secondary spongiosa, and a 13.1% increase in trabecular number and a 15.8% increase in trabecular thickness. | 213 |
| Mice | 8, 12, 20 weeks, female | Tibia | 2 Hz | 2–13 N | 40 per day | 10-s intervals between each cycle, for 2 weeks | For 12- and 20-week-old mice, loading induced significant decreases in BV/TV. In contrast, tibiae of younger 8-week-old mice show significant increases in BV/TV, achieved predominantly via increases in trabecular number. | 27 |
| Mice | 10, 26 weeks, male | Tibia | 4 Hz | 4.5/9.0 N | 1 200 per day | 1, 2, and 6 weeks | In both adult and young mice, loading at 9 N decreased epiphyseal bone mass with a greater decrease observed in the adult mice compared with the young mice. Bone mass increased by 20% with loading in young mice. | 31 |
| Mice | 26 weeks, female | Tibia | 4 Hz | 11.3 ± 0.5, 5.9 ± 0.5, and 1.5 ± 0.6 N | 1 200 per day | 5 days per week, for 2 weeks | After loading, cancellous bone mass increased 54% through trabecular thickening, and cortical area increased 41% through medullary contraction and periosteal expansion. Adult mice were able to respond to an anabolic stimulus and recover bone mass to levels seen in growing mice; however, the adaptive response was reduced relative to that in 10-week-old female mice for the same applied load. | 32 |
| Rats | 36 weeks, female | Tibia | 2 Hz | 27, 33, 40, 52, and 64 N | 36 per day | 12 days | Bending strains above a loading threshold of 40 N or about 1 050 mu strain increased both bone-forming surface and the mineral apposition rate and subsequently increased the bone-formation rate as much as six folds. No evidence of increased bone formation was seen for applied strains below 1 050 mu strain. | 170 |
F frequency for loading, Ref. references, n/a not available