**5. Mesenchymal stem cells**

*Recent Advances in Bone Tumours and Osteoarthritis*

effect of salicylate modifies the neurogenic control of inflammation, which may be abnormal in diseases that affect musculoskeletal structures such as OA [106, 107]. Changes in the expression and transport of neurogenic peptides may be induced by the local irritant effect of salicylate [108]. Systemic anti-inflammatory effects are unlikely, since the benefits are generally not observed in distant sites [105].

There is a degree of overlap between TPI and acupuncture in that the injection sites are standard acupuncture locations. Acupuncture involves the insertion of fine filiform needles at or near the tender anatomical site or sometimes at distant acupuncture "points". In a variation of this, the needles are sometimes stimulated electronically or with heat. Patients typically receive six or more sessions for a complete course of treatment. A systematic review of 393 patients with OA found acupuncture significantly improved pain but not function when compared to sham acupuncture [109–116]. In addition, results were no better than standard treatment with physiotherapy or being on a waiting list to receive acupuncture [109, 112]. There was also no additional benefit seen when using acupuncture as an adjunct to standard therapy with exercise and advice [115]. Moreover, there is little evidence for long-term benefit following acupuncture treatment, as symptomatic improvements tend to last up to 12 weeks only [109, 112]. Acupuncture is relatively safe,

Osteoarthritic joints may be reinforced by various forms of external support known as orthoses. These applied devices modify the structural and functional characteristics of the neuromusculoskeletal system. Benefit can be obtained by adjusting alignment, reducing stress or load, providing shock absorption or simply

Orthoses such as braces, splints and elasticated sleeves are frequently used in OA of the hand and knee. Thumb and wrist splints are employed in hand OA, whilst knee sleeves and unloading braces can be useful adjuncts in knee OA. Medial patellar strapping can be specifically helpful for patellar maltracking [117]. Shoe insoles may be of benefit in OA affecting the ankle and knee and can sometimes alleviate symptoms caused by OA of the hip. Insoles can be differentiated into cushioned or neutral subtypes, which have shock-absorbing properties, and wedged insoles, which offset varus or valgus deformities as well as modulate mechanical stress. For OA of the knee and ankle, the main purpose of orthoses and insoles is to support a joint that is unstable and to help correct alignment [118]. They can modify load bearing, contribute to pain reduction and improve physical function. There is also some evidence that they can improve proprioception [119] and they may slow disease progression [120]. They are especially useful for mild or moderate uni-compartmental knee OA where there may be varying degrees of instability and

Unloading knee braces are designed to reduce the load transmitted to the affected compartment by applying an external valgus or varus force. Symptomatic relief is achieved by stabilising the joint, increasing joint opening and reducing local muscle contraction [120]. One study [123] demonstrated that patients with medial compartment knee OA treated with unloading knee braces had better functional and symptomatic outcomes at 6 months. These results were not replicated in other studies [124] although there is evidence they can improve quadricep strength and

The main disadvantage of these braces is poor tolerability due to the weight and heat of the device. In one study, 41% of patients complained of skin irritation [126],

however, with minimal risks of serious side effects [113–116].

**116**

**4. Orthoses**

resting the joint.

malalignment [121, 122].

gait symmetry [125].

The next frontier in local osteoarthritis management is likely to involve the use of mesenchymal stem cells (MSCs). These pluripotent cells have the capacity to differentiate into a variety of cell types, including chondrocytes, making their potential use in osteoarthritis a highly attractive prospect [132].

MSCs can undergo chondrogenesis and have been combined with a number of materials that support this differentiation, including the aforementioned polymer HA [133]. Neocartilage formation, hypertrophy and matrix calcification, as is seen in the terminal differentiation of hypertrophic chondrocytes in the growth plate, have been observed in vitro [134] and in mice [135] resulting in the efficient formation of bone. There are various hypotheses as to how this might occur. They include the inhibition of apoptosis [136] and subsequent immunomodulation [137] both of which are currently being tested in murine models of OA.

Clearly, translation to human studies is required before MSCs become a viable clinical option in the local treatment of OA, but there is understandable optimism that this therapy may herald a long-term solution to slowing the rate of articular cartilaginous degeneration and subchondral bone remodelling.

### **6. Conclusion**

There are numerous local treatments for osteoarthritis. The majority of local therapies are safe and avoid any significant systemic adverse effects. They mostly provide symptomatic relief. In many cases this is of undoubted value to individual patients, particularly during the inflammatory phase of OA. In some cases there may be a useful placebo effect. In general, these therapies should be used as adjuncts to physiotherapy and systemic analgesia which remain the mainstay of conservative OA management. The choice of local therapy in an individual patient should be guided by the severity of disease, local experience and patient preference.

Some of these treatments, for instance, IA injections and orthoses, are well established and have been used in clinical practice for many decades. Other more novel approaches have been developed such as local laser therapy and subcutaneous sodium salicylate injections. However, for all the therapies described in this chapter, there are only limited data to demonstrate long-term benefit. Further studies are required to establish their lasting value. In the meantime these treatments remain valuable as temporary measures for many patients, particularly those with flares of symptoms or who are awaiting more definitive treatment.

*Recent Advances in Bone Tumours and Osteoarthritis*
