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Wolff's law in action: a mechanism for early knee osteoarthritis.

Teichtahl AJ, Wluka AE, Wijethilake P, Wang Y, Ghasem-Zadeh A, Cicuttini FM - Arthritis Res. Ther. (2015)

Bottom Line: Wolff's law theorizes that repetitive loading of bone will cause adaptive responses enabling the bone to better cope with these loads.Similarly, fractal analysis of bone architecture provides further clues that bone adaptation may have untoward consequences for joint health.A potential disease paradigm to account for such a hypothesis is also proposed, and novel therapeutic targets that may have a bone-modifying effect, and therefore potentially a disease-modifying effect, are also explored.

View Article: PubMed Central - PubMed

Affiliation: Baker IDI Heart and Diabetes Institute, 99 Commercial Road, Prahan, VIC, 3004, Australia.

ABSTRACT
There is growing interest in the role of bone in knee osteoarthritis. Bone is a dynamic organ, tightly regulated by a multitude of homeostatic controls, including genetic and environmental factors. One such key environmental regulator of periarticular bone is mechanical stimulation, which, according to Wolff's law, is a key determinant of bone properties. Wolff's law theorizes that repetitive loading of bone will cause adaptive responses enabling the bone to better cope with these loads. Despite being an adaptive response of bone, the remodeling process may inadvertently trigger maladaptive responses in other articular structures. Accumulating evidence at the knee suggests that expanding articular bone surface area is driven by mechanical stimulation and is a strong predictor of articular cartilage loss. Similarly, fractal analysis of bone architecture provides further clues that bone adaptation may have untoward consequences for joint health. This review hypothesizes that adaptations of periarticular bone in response to mechanical stimulation cause maladaptive responses in other articular structures that mediate the development of knee osteoarthritis. A potential disease paradigm to account for such a hypothesis is also proposed, and novel therapeutic targets that may have a bone-modifying effect, and therefore potentially a disease-modifying effect, are also explored.

No MeSH data available.


Related in: MedlinePlus

Hypothesized disease paradigm for early traumatic secondary knee osteoarthritis (OA). ACL anterior cruciate ligament, BMD bone mineral density
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Fig1: Hypothesized disease paradigm for early traumatic secondary knee osteoarthritis (OA). ACL anterior cruciate ligament, BMD bone mineral density

Mentions: Although OA is a heterogeneous disease with multiple pathways of varied etiologies leading to a common endpoint of joint damage, we propose a “bone adaptation” paradigm with a common final pathway of cartilage damage in both primary and secondary knee OA. In secondary knee OA, we base our disease paradigm on evidence collated from animal studies which, via trauma, induce OA (Fig. 1). An initial acute insult to the knee, such as an ACL rupture, leads to a sudden overburdening of periarticular bone and a resorptive phase [28, 29]. This may initially cause a transient “osteoporosis-like” state, as has been demonstrated in dog and mouse models of OA [28, 29]. This overburdening of periarticular osteoporotic bone may result in microfractures and a compensatory shift toward an osteoblastic state to promote fracture healing that ultimately results in an increase in periarticular BMD [28, 29]. These changes therefore appear time-dependent. This is exemplified in a mouse model of OA, in which there was rapid loss of trabecular bone 7 days after knee injury. However, partial recovery of bone to a new state occurred by 28 days, and by day 56, considerable non-native bone formation had occurred [29]. Moreover, in a canine model, the regions of pronounced BMD loss corresponded to the area of focal cartilage defects [28]. In parallel with these changes, trabeculae network remodeling occurs with subsequent downstream effects on cartilage loss [49–51]. Therefore, although these adaptations may ultimately enable bone to better redistribute mechanical load, they inadvertently predispose cartilage degeneration. This may occur in part via impairment of flow of nutrients to the avascular hyaline cartilage via the sclerosed subchondral interface [54], thus setting up a trajectory of early knee OA.Fig. 1


Wolff's law in action: a mechanism for early knee osteoarthritis.

Teichtahl AJ, Wluka AE, Wijethilake P, Wang Y, Ghasem-Zadeh A, Cicuttini FM - Arthritis Res. Ther. (2015)

Hypothesized disease paradigm for early traumatic secondary knee osteoarthritis (OA). ACL anterior cruciate ligament, BMD bone mineral density
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4556408&req=5

Fig1: Hypothesized disease paradigm for early traumatic secondary knee osteoarthritis (OA). ACL anterior cruciate ligament, BMD bone mineral density
Mentions: Although OA is a heterogeneous disease with multiple pathways of varied etiologies leading to a common endpoint of joint damage, we propose a “bone adaptation” paradigm with a common final pathway of cartilage damage in both primary and secondary knee OA. In secondary knee OA, we base our disease paradigm on evidence collated from animal studies which, via trauma, induce OA (Fig. 1). An initial acute insult to the knee, such as an ACL rupture, leads to a sudden overburdening of periarticular bone and a resorptive phase [28, 29]. This may initially cause a transient “osteoporosis-like” state, as has been demonstrated in dog and mouse models of OA [28, 29]. This overburdening of periarticular osteoporotic bone may result in microfractures and a compensatory shift toward an osteoblastic state to promote fracture healing that ultimately results in an increase in periarticular BMD [28, 29]. These changes therefore appear time-dependent. This is exemplified in a mouse model of OA, in which there was rapid loss of trabecular bone 7 days after knee injury. However, partial recovery of bone to a new state occurred by 28 days, and by day 56, considerable non-native bone formation had occurred [29]. Moreover, in a canine model, the regions of pronounced BMD loss corresponded to the area of focal cartilage defects [28]. In parallel with these changes, trabeculae network remodeling occurs with subsequent downstream effects on cartilage loss [49–51]. Therefore, although these adaptations may ultimately enable bone to better redistribute mechanical load, they inadvertently predispose cartilage degeneration. This may occur in part via impairment of flow of nutrients to the avascular hyaline cartilage via the sclerosed subchondral interface [54], thus setting up a trajectory of early knee OA.Fig. 1

Bottom Line: Wolff's law theorizes that repetitive loading of bone will cause adaptive responses enabling the bone to better cope with these loads.Similarly, fractal analysis of bone architecture provides further clues that bone adaptation may have untoward consequences for joint health.A potential disease paradigm to account for such a hypothesis is also proposed, and novel therapeutic targets that may have a bone-modifying effect, and therefore potentially a disease-modifying effect, are also explored.

View Article: PubMed Central - PubMed

Affiliation: Baker IDI Heart and Diabetes Institute, 99 Commercial Road, Prahan, VIC, 3004, Australia.

ABSTRACT
There is growing interest in the role of bone in knee osteoarthritis. Bone is a dynamic organ, tightly regulated by a multitude of homeostatic controls, including genetic and environmental factors. One such key environmental regulator of periarticular bone is mechanical stimulation, which, according to Wolff's law, is a key determinant of bone properties. Wolff's law theorizes that repetitive loading of bone will cause adaptive responses enabling the bone to better cope with these loads. Despite being an adaptive response of bone, the remodeling process may inadvertently trigger maladaptive responses in other articular structures. Accumulating evidence at the knee suggests that expanding articular bone surface area is driven by mechanical stimulation and is a strong predictor of articular cartilage loss. Similarly, fractal analysis of bone architecture provides further clues that bone adaptation may have untoward consequences for joint health. This review hypothesizes that adaptations of periarticular bone in response to mechanical stimulation cause maladaptive responses in other articular structures that mediate the development of knee osteoarthritis. A potential disease paradigm to account for such a hypothesis is also proposed, and novel therapeutic targets that may have a bone-modifying effect, and therefore potentially a disease-modifying effect, are also explored.

No MeSH data available.


Related in: MedlinePlus