Table 1. Collection of reference publications using in vivo axial loading, with details of loading waveforms, loads, strains and observed effects on bone.
| Species | Strain | Gender (M/F) | Site | Age (weeks) | Waveform | Peak load (N) | Peak strain (μɛ) | Strain rate (μɛ s−1) | Pulse period (s) | Rest period (s) | Frequency (Hz) | Nb cycles/session | Schedule | Observations (Only WT/non-treated/controls) | Reference |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Rats | Spargue Dawley | F | Ulna | 10±2a | Sine | 15 and 20 | 3125 | NA | NA | NA | 10, 20 | 1200, 12 000 | Day 5, 6, 8, 11, 12, 13, 14 and 15 | First introduction of in vivo axial loading. Osteogenic response with 20N: decelerated modeling drift, increased cross-sectional area, increase in periostal formation. New bone formation proportional to surface strains. Small or no repsonse with 15N. | Torrance et al.19 |
| Rats | Fisher | F | Ulna | 32 | Haversine | 13.3 | 2400 | NA | NA | NA | 2 | ∼8000 | Day 1 | Periostal bone formation at 6, 12 and 18 days. Stiffness and toughness loss of 50% and 70%, respectively at day 0, equivalent to controls at day 12, increased +20% at day 18. | Hsieh and Silva,40 |
| Mice | C57Bl/J6 | F | Tibia | 8, 12 or 20 | NA | 2 to 13 | NA | 0.002 | NA | 10 | 2 | 40 | 3 Days per week for 2 weeks | Between 8 and 12 N, significant increased periosteal inter-label; load-related increase in cortical new bone formation. Response to 13N equivalent to 12 N. No effect below 8 N. | De Souza et al.21 |
| Mice | C57BL/6J | M | Tibia | 14±1 | Trapeze | 12 | 1500 | NA | 0.1 | 10 | 0.1 | 40 | 3 Days per week for 2 weeks sacrificed 3 days later | Increased bone mineral density and biomechanical properties of long bones; increased bone formation activity, particularly at the periosteum. Enhanced trabecular and cortical microarchitecture. | Bonnet et al.11 |
| Mice | C57BL6 | M | Tibia | 17±1 | Square | 8 | 1900 | 80 000 | 0.25 | 0.25 | 2 | 120 | Day 1, 3, 5, 8 and 102 × per day | Localized increase of cortical thickness and bone area; Stiffness of tibia increased by 16% compared with control, but no effect on ultimate force and postyield energy to failure. | Stadelmann et al.25 |
| Mice | C57BL/6 C3H/HeJ and DBA/2J | F | Ulna Tibia | 16 | Haversine | Strain adjusted | 2000 | NA | NA | NA | 2 | 99 | 3 Days per week for 3 weeks | Tibiaes showed greater MS, MAR and BFR than ulna at equivalent strains. No significant breed-related differences found in response to loading. | Kuruvilla et al.45 |
| Mice | C57BL/6 | F | Tibia | 17 | Triangle | 2 to 14 | 700 to 5000 | up to ∼ 75 000 | 0.05 | 10 | 0.1 | 40 | Day 5, 7, 9, 11, 13, 15, 17, and 19 | Woven bone formation at the proximal and midshaft on lateral and posterior surfaces tibia with 5000 μɛ loading. Strength adaptation of tibia to peak dynamic loads proporational to peak load. | Sugiyama et al.23 |
| Mice | C57BL/6 | F | Tibia | 19 | Trapeze | 13.5 | 1400 | ∼50 000b | 0.05 | 10 | 0.1 | 40 | 3 Days per week for 2 weeks | Increased proximal trabecular bone fraction, proximal cortical volume and midshaft cortical volume in tibia. Increased midshaft cortical bone volume in fibula. Woven bone formation. No systemic effects. | Sugiyama et al.43 |
| Mice | C57BL/6 | F | Tibia | 19 | Trapeze | 13.5 | 1800 | ∼50 000c | 0.05 | 10 | 0.1 | 40 | 3 Days per week for 2 weeks | In cortical bone, decreased osteocyte sclerostin, increased bone formation and bone volume proximal but not distal. In trabecular bone, decreased osteocyte sclerostin and increased bone volume in secondary spongiosa. | Moustafa et al.46 |
| Mice | C57BL/6 | F | Tibia | 16 | Haversine | 5, 7 and 9 | 1833 | NA | NA | NA | 2 | 360 | 3 Days per week for 4 weeks | In cortical bone, load-related response, up to 42% increase in midshaft pMOI with 9N. In trabecular bone, no response with 5 and 7N. With 9N, proximal BV/TV increased by 31%. | Weatherholt et al.47 |
| Mice | C57Bl/6 | F | Tibia | 26 | NA | 6 and 11.5 | 1200 and 2100 | NA | NA | 0.1 | 4 | 1200 | 5 Days per week for 2 weeks (Days 1–5, 8–12)d | With 11.5N, trabecular mass increased by 54% through trabecular thickening, cortical area increased by 41% through medullary contraction and periosteal expansion. No effect with 6N. | Lynch et al.48 |
| Mice | C57Bl/6 | F | Tibia | 8 | Haversine bouts (4 cycles followed by 3s pause) | 8.8, 10.6, and 12.4 | 1700, 2050 and 2400 | NA | NA | 3 | 2 | 220 | 14 day period with a day of rest after every third day of loading, resulting in 9 loading days | Load-related improved bone architecture. No effect with 8.8 N. With 10.6N improved cortical and trabecular bone, improved mechanical properties. With 12.4 N half of animals show woven bone response. | Berma et al.49 |
| Mice | BALB/c | M | Tibia | 28 and 88 | Triangle | 8, 10, and 12 | 3100 | 48N s−1 | 0 | 10 | ∼0.1 | ∼12 000 | 5 Days per week for 1 weeks (Mon-Fr)e | Strong anabolic response on midshaft endocortex and periosteum for both age groups. Aged mice show greater endocortical response than young adult. | Brodt et al.50 |
| Mice | BALB/c | F | Tibia | 8, 16, 28 and 48 | Triangle | 7.5, 10, 8.5 and 11 | 1300 | 48N s−1 | 0 | 10 | ∼ 0.1 | 60 | 3 Days per week for 1 or 6 weeks | After 1 week, no effect in 8-w-old mice but increased osteoblast/matrix genes in older mice. After 6 weeks, increased cortical bone volume at all ages. | Silva et al.51 |
| Mice | C57BL/6 and BALB/c | F | Tibia | 16 | Triangle | 10 | 2800 in BL6 2350 in BALBc | NA | NA | 100.1 | 26.7 | 60 (WashU) 1200 (Cornell) | 3 Days per week for 6 weeks | Compared WashU and Cornell/HSS protocols. Anabolic cortical bone response with both, but Cornell/HSS more rapid response (+ 13%). Mouse strain had no influence. | Holguin et al.52 |
Abbreviations: BV/TV, bone volume/total volume; F, female; M, male; NA, not applicable.
aEstimated from Charles River growth chart based on reported weight of 200–220 g.
bEstimated from reported data.
cSame experiment as Sugiyama et al. -> We assume same strain.
dAlso known as Cornell/HSS protocol.
eAlso known as WashU protocol.