Orthobiologic considerations in tissue degradation, repair and regeneration. Part 2
Musculoskeletal Ageing and Degeneration
Musculoskeletal ageing and degeneration during the life course affects the quality and length of life. Some of the primary features involve - loss of bone, weakened degradative joint cartilage and narrowed intervertebral discs which all contribute to pain and loss of functional mobility.
The Ageing Skeleton
In the ageing skeleton, bone volume and mass declines and in some cases can lead to osteoporosis and an increased risk of fracture. Loss of joint cartilage thickness with age often leads to osteoarthritis, while decreasing structural integrity within the intervertebral discs (IVDs) leads to loss of disc height, and collapse and compression within the spine.
With individual tissues, there is a delicate cellular balance which is matched to the local requirements. In the ageing skeleton, the effects of reduced bone cell formation activity are compounded by increased bone cell destruction formation and function. The resulting excessive bone destruction reduces skeletal volume and strength and predisposes to increased risks. Hormones also play a key role in bone biology; in women, the decline in oestrogen levels following menopause leads to a dramatic loss of bone strength. Bone formation rate is insufficient to match the excessive destruction by overstimulated bone destruction cells in the natural remodelling of bone tissue. In men, low levels of androgens also attribute to bone ageing.
Ageing joint cartilage undergoes changes to structure with some. The most notable changes are a decrease in water content and decreases of the core protein of the main PG and chondroitin sulphate. As a result the cartilage cannot deal with compressive forces as well. Furthermore, little is known about oxygen tensions within the avascular environment of articular cartilage. Cartilage cells (chondrocytes), although suited to a low oxygen environment, do consume much lower levels of oxygen in comparison to other cells. However, how chondrocytes use oxygen is unclear. They contain a very low number of mitochondria compared to most other cell types, and derive most of their energy from an oxygen-independent process via a pathway of glycolysis. The supply of oxygen, as well as of other nutrients, reaches the cartilage not only from the synovial fluid (which is in turn supplied by the vasculature of the joint capsule and the synovium) but also from the subchondral bone. Age-related changes in the subchondral bone, which often undergoes significant remodelling, would probably affect the oxygen tension in the joint, as would increasing calcification of the cartilage itself, which has also been associated with advancing age.Like other tissues including bone, articular cartilage appears to be susceptible to damage caused by oxidative stress.
Spinal discs are composed of a central highly hydrated tissue named the nucleus pulposus. This is surrounded by a fibrous ring, the annulus fibrosus. Both tissues are enclosed between the vertebral endplates. The first signs of disc degeneration start early in life and mainly affects nucleus. Disc dehydration then further leads to reduced functional support and further degradation. As the disk reduces its capacity of fully dealing with compressive forces, the bone begins to take more compressive load, which, it is ultimately not designed for. Bone begins to then grow out laterally, distributing the weight over a larger surface area. This, unfortunately predisposes bone spurs which can cause many complications.
In summary, the musculoskeletal system is a dynamic environment consisting of a variety of tissues types made up of several different cellular components within complex arrangements. The interaction of each tissue type is essential for the adequate functioning of the skeleton as a whole, and as such, each region (bone, cartilage, tendon, disc, muscle vasculature) has the potential to significantly affect the others. As we age, the alterations in normal biological responses lead to impaired tissue function, manifest in features we recognise as ageing. This is especially true in the musculoskeletal system, where the interdependent nature of skeletal components is particularly susceptible. Ongoing investigations identifying, characterising, and targeting novel ageing-related mechanisms may serve to increase health-span, lengthen lifespan, and prevent musculoskeletal deterioration as we age.
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