Unfortunately, there is a dearth of relevant published clinical data to allow one to answer this question with real confidence for a patient with knee OA in Europe or North America, and none that I know of for patients in India.

In a UK study¹ of 490 patients over the age of 40 years with knee OA awaiting joint replacement surgery, the age, sex and knee pain adjusted odds ratios for radiographic knee OA in 737 siblings were 2.9 (95% confidence interval 2.3–3.7) for tibiofemoral OA and 1.7 (95% CI 1.4–2.2) for patellofemoral OA compared with 1729 community controls, but the risk of hip OA in the siblings was not studied. The 2–3-fold increased risk of knee OA in the siblings persisted after adjustment for environmental risk factors, suggesting that it was genetically determined. Heritability was higher in men (0.78) than in women (0.49) and this may in part explain why the overall estimate of heritability of knee OA in this study was higher (62%) than the widely quoted figure of 39%, which comes from a classical twin study which was restricted to women.² These are, however, just estimates of the relative risk of radiographically defined knee OA in siblings. If one considers that approximately 10% of people >55 years of age in the UK have knee OA with pain and severe disability,³ it is likely that the sibling of a patient with significant knee OA has a 20–30% risk of developing painful and disabling knee OA in later life.

Good information on risk in offspring is even sparser. In the US Framingham Offspring Study of 337 nuclear families with two parents and at least one adult biologic offspring, 42% of the parents (mean age 73 years) and 22% of the offspring (mean age 54 years) had radiographic evidence of mild knee OA.⁴ There was a correlation (r) of 0.115 between parents and offspring for generalized radiographic OA, but there are no published data on the frequency of knee or hip OA in the offspring of parents with knee osteoarthritis.

Heritability of OA is higher in families where the disease begins before the age of 40 years, at least in part because of the occurrence of hereditary osteochondrodysplasias such as multiple epiphyseal dysplasia or spondyloepiphyseal dysplasia that lead to premature OA.  Patients and close family members with one of these rare Mendelian genetic disorders usually have multiple, as well as atypical joints affected, a history of symptoms beginning in childhood or adolescence and associated short stature or skeletal disproportion, as well as radiographic evidence of widespread skeletal abnormalities.

Standing radiographs of knees in a semiflexed position are certainly better than anteroposterior standing radiographs of fully extended knees, which were previously conventionally employed for assessing articular cartilage loss in patients with knee osteoarthritis.

With the knee in extension, the joint space width in the medial compartment of the knee reflects both the combined thicknesses of the femoral and tibial articular cartilage and that of the meniscus; whereas in the semiflexed position, the meniscus is excluded from the site of minimum joint space measurement in the medial compartment. In the extended knee position, the measurement plane of the joint space is outside the site of load transmission; while in the semiflexed knee, the articular cartilages are under direct load at the site where joint space width is measured. Accurate parallel radioanatomical alignment of the anterior and posterior margins of the medial tibial plateau is also crucial for optimal detection of joint space narrowing in serial X-rays in patients with knee OA.

A number of methods have been employed to standardize the radioanatomical position of the knee in longitudinal studies of disease progression and in trials of possible structure-modifying drugs. Some, such as the semiflexed AP view and the Lyon Schuss view, involve fluoroscopically assisted positioning of the knee, while others, such as the semiflexed posteroanterior metatarsophalangeal view and the posteroanterior fixed flexion view, use empirically derived standards for knee flexion and rotation.

For years I have held the view that progress in understanding the pathogenesis of osteoarthritis was severely limited by the concept that it was a single disorder resulting from attrition of articular cartilage by the inevitable processes of aging, wear and tear.⁷ There is now an abundance of evidence that osteoarthritis is not uniquely a progressive degenerative disease of articular cartilage, but rather the end result of a number of processes that lead to organ failure of diarthrodial joints.

Pathological studies have demonstrated that all of the tissues of the joint are usually involved and regenerative changes, as in osteophytes, as well as degenerative changes are characteristic features. Whereas in many cases, the initial pathology appears to be a degeneration of articular cartilage, in others it is pathological changes in the subchondral bone, the synovium, the supporting ligaments and muscles, or neurological problems that drive the process. The evidence for this is well described in the chapter on pathogenesis of OA in the second edition of the monograph osteoarthritis,⁸ and by Denis McGonagle,⁹ who has suggested a novel anatomical classification of OA based on the tissue of origin.

There is good research evidence that both quadriceps-strengthening exercises and more general lower limb muscle-strengthening exercises are effective in reducing pain and in improving physical function in patients with symptomatic knee OA,¹⁰ and they are recommended in the recent EULAR recommendations for the non-pharmacological core management of knee OA.¹¹ Hip-strengthening exercises have also been shown to reduce knee pain and improve physical function in patients with medial tibiofemoral OA of the knee.¹²

Although I have to confess to complete ignorance of yogic practices, or the muscle strengthening that ensues, I know of no evidence that might suggest that specific strengthening of the hamstrings would protect against the development of knee OA. Many years ago, Slemenda et al. showed that quadriceps, but not hamstring, muscle weakness was commonly associated with knee OA, and that quadriceps weakness predicted the development of symptomatic and radiographic OA of the knee.¹³ More recently, data from the US Multicenter Osteoarthritis (MOST) study demonstrated that while subjects with the highest tertile of knee extensor (quadriceps) strength had some protection from developing symptomatic knee OA, neither quadriceps muscle strength nor the balance of quadriceps to hamstring strength protected subjects from developing incident radiographic knee OA.¹⁴

It has been my practice to explain to patients with knee OA that contact forces in their knee increase by about 3.5 times body weight when climbing stairs¹⁵ and that stair climbing and squatting will increase knee pain and biomechanical stress in their tibiofemoral joints, especially if they are obese and have a bow leg, varus, and deformity. If they have anterior patellofemoral pain, I also tell them that squatting can induce considerable shear stresses across their patellofemoral joints.¹⁶ Because of this, it seems to me to make sense to try and counsel patients to avoid excessive stair climbing or squatting even though there is no evidence that these activities are risk factors for either the incidence or the progression of knee OA. I do, however, put greater emphasis on the need for muscle strengthening and aerobic exercise and on the importance of weight reduction in patients who are overweight or obese. Regrettably, I really do not know what are the biomechanical effects in knees of cross-leg sitting. Although it is frequent activity in India, it is seldom an issue for osteoarthritis patients in the UK.

It is difficult to be certain at the present time whether ‘erosive OA’ is a truly distinctive subset of hand osteoarthritis, as was postulated when it was first described,¹⁷ or whether it is just a more severe and aggressive manifestation of nodal osteoarthritis.¹⁸ A combination of subchondral erosion and proliferative bone remodelling give rise to the characteristic ‘gull’s wing’ radiographic appearance, which is distinct from the marginal erosions that occur in rheumatoid arthritis and the punched out lesions with overhanging margins that are associated with tophaceous gout, but they do seem to be just at the severe end of a spectrum of changes observed in X-rays of patients with nodal OA. While it was formerly thought that, unlike nodal OA, erosive hand OA was not associated with generalized osteoarthritis, recent studies have shown association with subchondral bone attrition in the knee,¹⁹ clinical overlap, and frequent association with components of the metabolic syndrome.²⁰

No, there have been no therapeutic trials that I know of and I do not see any indication for using bisphosphonates or Dkk inhibitors for the treatment of early diffuse idiopathic skeletal hyperostosis (DISH). Although patients with DISH, particularly elderly men, are at an increased risk of sustaining vertebral fractures, there is no evidence for associated osteoporosis,²² as there is in patients with ankylosing spondylitis. It seems likely that the increased risk of spinal fractures in DISH results from loss of elasticity in the ossified paraspinal ligaments rendering patients more susceptible to biomechanical stresses.

Florid inflammation with flares of severe pain, swelling, effusion and all the clinical signs of inflammation are rather rare in patients with uncomplicated knee osteoarthritis and such episodes should always be investigated with synovial fluid analysis to exclude superimposed joint infection or crystal-induced inflammation (CPPD-associated pseudogout or MSU-associated true gout). Some evidence of inflammation is, however, frequently observed in majority of patients with symptomatic knee OA and in many patients with radiographic evidence of knee OA, even at times when they are free from knee pain. In a large EULAR study of patients with painful knee OA, one-third of them had clinical effusions and half had evidence of synovitis or effusion on ultrasound.²⁴ In another study, 95% of patients with knee OA and effusions and 70% of those without effusions had evidence of synovitis using MRI.²⁵

Differentiation from RA or other types of inflammatory joint disease is usually achieved by taking a careful clinical history, examining the patient for evidence of more widespread joint involvement, signs of systemic illness, extra-articular features and routine blood tests to look for evidence of an acute-phase response and/or positive serology. Synovial fluid in OA is mostly clear and viscous with a low cell count (<2000/mm3) of predominantly mononuclear cells but these characteristics are variable and lack specificity. Synovial biopsies are seldom indicated unless there is concern about the possibility of a tuberculous infection or a foreign body granuloma following a penetrating injury. Biopsies from patients with inflammatory knee OA generally show less lymphocyte and plasma cell infiltration of the synovium and less in the way of perivascular aggregates than in RA, but are sometimes indistinguishable. Imaging with ultrasound or MRI can be more discriminating and helpful diagnostically in difficult cases.