Monthly Archives: April 2017

Fatigue Loading may be important to LSJL

This paper shows that axial loading can induce an almost complete line through the bone through one side to the other.  But the break is on the wrong axis.  If fatigue loading was induced via transverse loading (lsjl) it is very likely that the micorodamage would be along the right axis.  But induce bone fatigue in this way would likely require heavier loads than inducing sufficient hydrostatic pressure to induce chondrogenesis.

Role of Calcitonin Gene-Related Peptide in Bone Repair after Cyclic Fatigue Loading

“We used the rat ulna end-loading model to induce fatigue damage in the ulna unilaterally during cyclic loading. We postulated that CGRP would influence skeletal responses to cyclic fatigue loading. Rats were fatigue loaded and groups of rats were infused systemically with 0.9% saline, CGRP, or the receptor antagonist, CGRP8–37, for a 10 day study period. Ten days after fatigue loading, bone and serum CGRP concentrations, serum tartrate-resistant acid phosphatase 5b (TRAP5b) concentrations, and fatigue-induced skeletal responses were quantified. cyclic fatigue loading led to increased CGRP concentrations in both loaded and contralateral ulnae. Administration of CGRP8–37 was associated with increased targeted remodeling in the fatigue-loaded ulna. Administration of CGRP or CGRP8–37 both increased reparative bone formation over the study period. Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP8–37 administration.”

“sensory innervation of bone may have regulatory effects on skeletal responses to bone loading”

“Periosteum, endosteum, and bone tissue are all innervated by nerve fibers. This innervation exhibits plasticity in response to mechanical loading, in that a single loading event results in persistent changes in neuropeptide concentrations in both loaded and distant long bones, as well as changes in the neural circuits between limbs”

“Individual bone cells are directly connected to the nervous system via unmyelinated sensory neurons. Bone cells express a range of functional neurotransmitter receptors and transporters, including those for calcitonin gene related peptide (CGRP)”

“12 rats were fatigue loaded until 40% loss of stiffness was attained, using an initial peak strain of −3,000 µε (Fatigue group). ”

“To induce fatigue, the load applied to the ulna was incrementally increased until fatigue was initiated, as indicated by increasing displacement amplitude from a stable baseline. ”

The break extends all along the bone but is on the wrong axis.
“Increased bone blood flow precedes bone repair in response to fatigue loading, and remodeling in response to decreased mechanical loading . Systemic administration of CGRP also decreases blood pressure in a dose-dependent manner””
“”treatment with CGRP8–37 may have increased intraosseus pressure, transcortical interstitial fluid flow, and associated bone formation””

Impact loading on mouse bone length

Normally, I wouldn’t draw attention to this first paper but it draws an interesting thought:  “That long term sustained loading is better for longitudinal bone growth, whereas short term intense loading is better for bone quality.”  This could be due to hydrostatic pressure being good for stimulating a cartilagenous(and thus a pro growth plate micro-environment) whereas rapid changes in fluid flow as induced by short term dynamic loading(like jumping) are better for changes in bone quality.  So I will be changing the way I will be performing LSJL, rather focusing on clamping as hard as possible I will not be clamping as hard but doing longer more sustained clamps.

Enhancement of bone quality and longitudinal growth due to free-fall motion in growing rats

“[We] investigate the synchronous phenomena between bone quality and longitudinal length in a same subject affected by landing exercise. Physical exercise on the ground induces external loading to human body due to resistance from ground which can activate bone generation or remodeling. Especially, when the impact stimulation is applied to bone, it may improve bone quality and lengthening.
6-week-old male Wistar rats were randomly allocated to one of two conditions: free fall from 40 cm-height (I40; n = 7), and control (IC; n = 7). The impact stimulations were administered to the free fall groups, 10 times/day, and 5 days/week for 8 weeks. Structural parameters and longitudinal length of tibia were measured to quantitatively evaluate the variation in morphological characteristics and bone length with maturing.
The landing impact seems to be commonly effective on the enhancement of bone quality as well as longitudinal growth. However, the extent of enhancement may be more dominant in bone quality than longitudinal growth. On the other hand, the ratio of longitudinal growth seems to be dependent on the duration of stimuli whereas the enhancement of bone quality does not.
This study verified that free-falls exercise can be effective on the enhancement of bone qualities and promotion of vertical growth in long bones. We expect that it might be possible for the moderate impact stimulation to be proposed as an aid for prevention of bone loss and promotion of bone lengthening.”

” Bone cells accommodate to a customary mechanical loading environment, making
them less responsive to routine loading “<-thus possibly needing to cycle on and off a method of bone stimulus.  Although our goal is to target stem cells to form new growth plates and not necessarily bone cells.

“In comparison between two groups, there is no significant [differnece] at 4 week, whereas the values in I40 group exhibited slightly but significantly higher than that in IC at 8 weeks”  So there was a change in limb length but it took 8 weeks to notice a difference.  It would be interesting to see if impact loading could have an impact on animals without functioning growth plates.  If it could increase longitudinal bone growth in some other way.

the ratio of longitudinal growth seems to be dependent on the duration of stimuli whereas the enhancement of bone quality does not.”<-this is interesting maybe it’s more important to clamp for a long period of time than intensity of clamping.  This could a lot of sense if longitudinal growth is driven by fluid whereas bone mechanical parameters are driven by stimulation of osteocytes and bone cells.  Longitudinal bone growth could be driven by sustained hydrostatic pressure whereas bone quality could be driven by rapid changes in interstitial fluid flow.

Another study found “. observed significantly greater increase in bone length compared to the sedentary rats when they implemented the similar training 100 times/day in 5 days/week
on Fisher 344 rats of 3-month-old and 6-month-old for 8 weeks”

Here’s that other study:

Effects of Jump Training on Bone Hypertrophy in Young and Old Rats

“The effects of jump training on bone hypertrophy were investigated in 3, 6, 12, 20 and 27 month-old female Fischer 344 rats. The rats of all age groups were divided into jump training
(height: 40 cm, 100 times/day, 5 days/wkfor 8wks), run training (speed: 30 m/min, 1 h/day, 5 days/wk for 8wk) or sedentary group. Fat-free dry weights (FFW) of the femur and the tibia were significantly greater in the jump-trained rats than in the runtrained rats, and were significantly greater in the run-trained rats than in the sedentary rats. jump training significantly increased FNV of the femur and the tibia not only in young rats but also in old rats, while run training did not increase FFW significantly in old rats. In young rats, both jump training and run training significantly increased the length of the femur and the tibia and the diameter of the femur. The diameter of the tibia was greater in the jump-trained rats than in the sedentary and the run-trained rats in all age groups. The results of the present study indicate that jump training was a more effective training mode than run training for bone hypertrophy and that the effects were not limited by age. ”

According to the chart, Jump training increased length of the tibia and femur on rats younger than 12 months but actually decreased tibia and femur length on rats older than that.  So the compressive force actually denatured the tibia and femur such that it was shorter.

But in the study they do say ” In the 3 and 6 month-old rats, both jump training
and run training increased the length of the femur and the tibia and the diameter of the femur.”<-which is contrary to what the graph says.

Key LSJL studies about device design

FINITE ELEMENT ANALYSIS OF AN UNDER-ACTUATED ROBOTIC DEVICE FOR
KNEE LOADING APPLICATIONS

“Knee loading is one form of joint loading modalities, which potentially provides a therapeutic regimen to stimulate bone formation and prevent degradation of joint tissues. Healing of knee injuries is sensitive to many environmental stimuli.  Since mechanical stimuli are crucial for the growth, development, and maintenance of articular cartilage and bone, we have developed an innovative robotic knee loading device to achieve this goal. This device induces mechanical loading to stimulate articular cartilage and bone, and it potentially reduces the healing time of injuries such as bone fractures. The robotic device is an improved version over previous joint loading devices, in which loads are applied at specific points with non-uniform loading around the knee joint. In this paper, finite element analysis (FEA) of this robotic device has been presented that includes static structural analysis and modal frequencies of the device for two different material configurations used in the design. The design with ABS plastic material offers the desired margin of safety while reducing the weight and cost. ”

“The robotic device examined in this paper is designed for small levels of deformation. The intended displacement of the working device is small, a maximum of 13 mm. large
deformations are not recommendable as such deformations will critically affect the effective range of motion of device. “<-we may want larger deformations for our purposes.

” If the stresses are too high for the material selected, the device may yield, resulting in the failure of the device.”<-this can happen with a clamp without enough strength.”

” if very small magnitude of mechanical stimuli is applied fast enough then it may induce a cellular response”<-This is an interesting thought.  It’s very hard to produce a rapid mechanical stimuli physiologically.  How many bicep curls can you perform in one second?

“Osteocytes are the highly mechanosensitive cells which senses the resulting physical stimuli from mechanical forces applied on bones. They constitute of more than 90% of bone cells.
When rapid mechanical loading is applied at the end of long bone, the interstitial fluid present around the osteocytes pressurizes causing the fluid flow which creates hydrostatic
pressure throughout the bone. This hydrostatic pressure excites the osteocytes resulting in enhanced osteogenesis which decreases the healing time of the fractures, increases the bone density and will be helpful in treatment of osteoporosis and osteoarthritis”<-we want additional stimuli from the hydrostatic pressure we want hydrostatic pressure to degrade bone tissue reducing the constraining effect that bone tissue has on growth and we want the stem cells to become more fibrocartilagenous.

“To apply such a load, a device would need to have a means of producing a transverse force directly to the end of a long bone, such as at the knee. A cyclic force applied in such an area would force a slight shift of the fluid within the bone towards the opposite end of the bone in a controlled fashion”<-this is what we do with the clamp.  Produce a transverse(lateral) force directly to the end of a long bone.  It has the potential to be cyclic if you rotate and reverse the rotation of the clamp.  We may want more than a slight shift of fluid and we may not care if it’s in a controlled fashion or not.

“a maximum force of 40 N with the frequency range of 1 Hz to 5 Hz will have a promising effect on a human knee”<-Higher force may be needed for longitudinal bone growth.

” the efficacy of stimulating the osteocytes depended on the stress distribution on the knee. Based on this observation, it is projected that a position specific loading that provides a more
targeted force application on the knee is likely to further improve the efficacy of bone stimulation. It is hypothesized in that this targeted loading would contribute to the
improvement of new bone formation over a distributed loading modality. “<-maybe a smaller clamp pad and instead of clamping the knee as a whole clamping different epiphysis’ separately.  Although we don’t necessarily care about stimulating the osteocytes, we want to degrade bone tissue and stimulate stem cells.  The statement about more targeted loading still applies.

I can’t post an image of the device but look at fig 4 and 5.

” It can be seen that when maximum force of 20 N is applied on human knee, the maximum stress generated is 11.22 MPa. “<-Since around 10MPa is the chondrogenic stimulatory range this is a key pressure however you may need to degrade bone tissue as well.   The study does not indicate exactly where in the knee the stress was generated. This was for alluminum and steel.  Other materials were used and they were all in this same range.

FINITE ELEMENT ANALYSIS OF AN ELECTRO-MECHANICAL KNEE LOADING DEVICE

“When a cyclic but controlled load with a specific frequency is applied to the bones (femur and tibia) and surrounding tissues in the knee, it affects the osseous tissue causing physical deformations.  These deformations result in pressure gradient in the intramedullary cavity of the bone. Due to this pressure difference, there is a fluid flow of molecules and nutrients.
This will result in osteoblast differentiation; a phenomenon will initiate new bone formation or osteogenesis. This can be used as a healing technique in case of bone related injuries
like fractures or diseases like osteoarthritis and osteoporosis.”<-slightly more powerful prediction in this study where they predict osteoblast differentiation and physical deformations.  They mention a specific frequency being needed.

“When the device is loaded with a human knee, the inertial load resisting the driving force is considerable.”