Joint Loading Modality: Its Application to Bone Formation and Fracture Healing

[문형철]

골절 치유를 촉진시키기 위한 joint loading을 주는 방법과 강도에 대한 의문을 풀고 있다.

모든 자극은 올바른 방향과 올바른 강도, 주파수가 있어야 한다. 

- 자기장 자극, 초음파 자극, 고주파 자극 등 healing process를 촉진하는 자극을 줄때 항상 whole body vibration, axial loading, bending loading을 고려해서 시행해야.

- 또한 periosteal bone formation자극인지, endosteal bone formation자극인지를 고려해서 시행해야.

뼈에 부하를 줄때 두가지 bone formation이 발생한다

1. periosteal bone formation

2. endosteal bone formation

또 무엇을 알아내야 할까?

panic bird......

Abstract

Sports related injuries such as impact and stress fractures often require a rehabilitation program to stimulate bone formation and accelerate fracture healing. This review introduces a recently developed joint loading modality and eval‎uates its potential applications to bone formation and fracture healing in post-injury rehabilitation. 

- fracture healing 촉진, bone formation 자극프로그램이 필요

- 이 논문은 joint loading modality를 찾은 논문  그리고 뼈형성과 골절치유를 측정하는 논문. 

Bone is a dynamic tissue whose structure is constantly altered in response to its mechanical environments. Indeed, many loading modalities can influence the bone remodeling process. The joint loading modality is, however, able to enhance anabolic responses and accelerate wound healing without inducing significant in situ strain at the site of bone formation or fracture healing. This review highlights the unique features of this loading modality and discusses its potential underlying mechanisms as well as possible clinical applications.

- 뼈는 기계적 환경에 따라 변화하는 dynamic tissue

- 정말로, 많은 부하형태는 뼈형성과정에 영향을 줄 수 있음. 

- 그러나 관절 부하형태는 동화반응과 손상치유촉진을 어떻게 할 수 있는가에 대한 것임. 

-  이 논문은 부하형태의 독특한 특성과 기저메카니즘에 대한 토의임.  

INTRODUCTION

Bone is a metabolically active tissue capable of adapting its structure to varying biophysical stimuli as well as repairing structural damage through remodeling. Daily activities enhance its mechanical strength,1–3 and physical exercises such as swimming,4, 5 climbing,6, 7 jumping, 8, 9 and running10, 11 can increase bone mass, density, and strength. Those activities or exercises are, however, mostly performed by healthy individuals12–15 and their efficacy depends on an individual’s weight, muscle strength, and fitness level. 

- 뼈는 적절한 자극에 의해 구조와 강도가 강해짐. 수영, 등산, 점프, 달리기 등은 bone mass, density, strength를 강화하는데 이는 건강한 성인에 적합한 프로그램. 

For sports-related stress fractures caused by continuous overuse and fractures caused by a blow or a fall, athletes are often required to participate in a rehabilitation program. Those programs typically enhance bone remodeling in a manner which depends on the needs of the individual. Thus, various loading modalities have been developed to extend the loading effects to sports-injured athletes as well as elders and also astronauts. The results of many load-driven bone adaptation studies16–18 have focused on in situ strain at the site of bone formation.19–21 Not only loading experiments but also exposures to unloading by disuse or spaceflight22 support the role of in situ strain in preventing bone loss. 

However, recent animal studies using non-habitual loads administered by joint loading indicate that in situ strain is not an absolute requirement for load-driven anabolic responses. This review explains this novel joint loading modality. Herein is described its potential applications for enhancing bone formation and accelerating fracture healing as well as increasing bone length. Two proposed mechanisms underlying joint loading-induced responses are presented and future research directions are suggested.

LOADING MODALITIES

Functional loading modalities

Representative loading modalities, which have been extensively studied in the last 10 or more years, include whole-body vibration,23, 24 axial loading 25, 26, and bending.19, 27 

1) Whole-body vibration applies oscillatory loads under 1 X G earth’s gravity, and dynamically disturbs the mechanical equilibrium state of bone. The strain magnitude induced by whole-body vibration depends on both the size of the applied load as well as the loading frequency. Whole-body vibration can induce anabolic responses mostly in trabecular bone with, for instance, ~ 200 μstrain at 90 Hz loading frequency.28 Axial loading and bending are generally applied to long bones such as ulnae and tibiae. 

2) Axial loading exerts principally longitudinal compression, while 3) bending generates lateral compression and tension. Since ulnae and tibiae are naturally curved, axial loading induces not only longitudinal stress but also a bending effect. In tibiae, for instance, axial loading29 and four-point bending30, 31 have been reported to induce a significant increase in bone formation mostly in load-bearing cortical bone.

참고) 올바른 자극과 방향을 적용하는 방법

- 자기장 자극, 초음파 자극, 고주파 자극 등 healing process를 촉진하는 자극을 줄때 항상 whole body vibration, axial loading, bending loading을 고려해서 시행해야.

- 또한 periosteal bone formation자극인지, endosteal bone formation자극인지를 고려해서 시행해야.

Role of dynamic strain

Based on previous animal studies with various loading modalities, it is generally accepted that bone adaptation occurs in response to dynamic (rather than static) loading. The effect of loading represents a composite of critical determinants including strain magnitude, strain rate, and number of loading cycles and bouts.20 In mouse ulna axial loading, for instance, dynamic strain above a certain threshold value (1000 – 2000 μstrain) is considered necessary to induce

detectable bone formation. Furthermore, the optimal range of loading frequencies is 5 – 10 Hz. 26 In whole-body vibration, in contrast, a significantly higher loading frequency (above 1 kHz) is considered to be effective with smaller strain (< 100 μstrain). 

- 이해가 안되네.. optimal range of loading frequency는 5~10Hz. 이게 먼말?

JOINT LOADING MODALITY AND BONE FORMATION

Elbow, knee and ankle loading

Joint loading is the most recently developed loading modality. It employs non-habitual loads applied to a synovial joint such as the elbow, the knee, and the ankle. Unlike other loading modalities, it does not appear to depend on load-induced strain at a site of bone formation.

Instead, loads are applied laterally to the epiphysis of the synovial joint and induction of bone formation is observed in the metaphysis and diaphysis of long bone.

Three forms of joint loading have so far been devised. Using a piezoelectric mechanical loader that can apply well-controlled loads at various waveforms, it has been shown in mouse studies that elbow loading,32, 33 knee loading,34–39 and ankle loading40 are able to induce bone formation in the ulna, tibia and femur, and femur (Fig. 1).

Five noteworthy characteristics of joint loading

Joint loading offers several unique features for mouse studies. 

First, it requires smaller loads to induce bone formation than most of the other loading modalities. In mouse studies, for instance, axial loading needs ~ 2 N force for elevating bone formation in ulnae, while 0.5 N force is sufficient with elbow loading.

- bone formation을 자극하는 최소한의 loading을 알아야. 예를들어 쥐실험에서 ulnae의 bone formation을 위해서는 axial loading 최소 ~2N force가 필요. 반면 elbow loading에서는 0.5N force이면 충분함

Second, joint loading is effective for inducing bone formation along the length of the entire long bone regardless of the longitudinal distance from the loading site. It has been shown that knee loading is able to induce bone formation not only in the distal diaphysis near the knee but also in the proximal diaphysis near the hip. Likewise, ankle loading is effective on the tibia along its length.40

- joint loading은 부하 위치로부터 멀어도 bone formation은 일어남. 

Third, compared to other loading modalities such as whole-body vibration, the number of required loading bouts is small. For instance, 1000 to 2000 bouts per day for 3 days are sufficient in mouse studies with in situ strain of ~ 10 μstrain. According to the predicted relationship between strain and the number of daily loading cycles, whole-body vibration requires approximately 200,000 bouts for loading with 10 μstrain.

- bone formation을 위한 number of required loading bouts is small. 예를덜어 1000~2000 bouts per day for 3days면 bone formation에 충분한 자극

Fourth, although the periosteal cortical surface is more sensitive than the endosteal surface, both surfaces are responsive to joint loading.37 It is, however, not well understood why the periosteal surface is more sensitive in most of the loading modalities (including joint loading) than the endosteal surface.

- periosteal cortical surface는 endosteal surface보다 sensitive하다. both surface는 joint loading에 반응. 

Fifth, a loading frequency of 2 – 15 Hz is effective, but existing data suggest that the optimal frequency differs among ulnae, tibiae, and femora.34, 35, 38 Geometry and dimension of each bone appear to affect frequency responses.

- loading frequency(부하 주파수)는 2~15Hz가 효과적. 

- ulnar, tibial, femur의 bone formation에 최적의 자극은 이미 연구되어 제시되어 있음. 

Diaphyseal bone formation in murine tibiae in response to knee loading. 2012년 논문

Diaphyseal bone formation in murine tibiae in response to k.pdf