title: Osteoarthritis and osteoporosis: clinical and research evidence of inverse relationship.
abstract: The etiology of osteoporosis (OP) and osteoarthritis (OA) is multifactorial: both constitutional and environmental factors, ranging from genetic susceptibility, endocrine and metabolic status, to mechanical and traumatic injury, are thought to be involved. When interpreting research data, one must bear in mind that pathophysiologic factors, especially in disorders associated with aging, must be regarded as either primary or secondary. Therefore, findings in end-stage pathology are not necessarily the evidence or explanation of the primary cause or event in the diseased tissue. Both aspects of research are important for potentially curative or preventive measures. These considerations, in the case of our topic--the inverse relationship of OP and OA--are of particular importance. Although the inverse relationship between two frequent diseases associated with aging, OA and OP, has been observed and studied for more than 30 years, the topic remains controversial for some and stimulating for many. The anthropometric differences of patients suffering from OA compared with OP are well established. OA cases have stronger body build and are more obese. There is overwhelming evidence that OA cases have increased BMD or BMC at all sites. This increased BMD is related to high peak bone mass, as shown in mother-daughter and twin studies. With aging, the bone loss in OA is lower, except when measured near an affected joint (hand, hip, knee). The lower degree of bone loss with aging is explained by lower bone turnover as measured by bone resorption-formation parameters. OA cases not only have higher apparent and real bone density, but also wider geometrical measures of the skeleton, diameters of long bones and trabeculae, both contributing positively to better strength and fewer fragility fractures. Not only is bone quantity in OA different but also bone quality, compared with controls and OP cases, with increased content of growth factors such as IGF and TGFbeta, factors required for bone repair. Furthermore, in vitro studies of osteoblasts recruited from OA bone have different differentiation patterns and phenotypes. These general bone characteristics of OA bone may explain the inverse relationship OA-OP and why OA cases have fewer fragility fractures. The role of bone, in particular subchondral bone, in the pathophysiology, initiation and progression of OA is not fully elucidated and is still controversial. In 1970, it was hypothesized that an increased number of microfractures lead to an increase in subchondral bone stiffness, which impairs its ability to act as a shock absorber, so that cartilage suffers more. Although subchondral bone is slightly hypomineralized because of local increased turnover, the increase in trabecular number and volume compensates for this, resulting in a stiffer structure. There is also some experimental evidence that osteoblasts themselves release factors such as metalloproteinases directly or indirectly from the matrix, which predispose cartilage to deterioration. Instead, the osteoblast regenerative capacity of bone in OP is compromised compared with OA, as suggested by early cell adhesion differences. The proposition that drugs which suppress bone turnover in OP, such as bisphosphonates, may be beneficial for OA is speculative. Although bone turnover in the subchondral region of established OA is increased, the general bone turnover is reduced. Further reduction of bone turnover, however, may lead to overmineralized (aged) osteons and loss of bone quality, resulting in increased fragility.
authors.affiliation: Department of Rheumatology, University Hospitals K.U.Leuven, Leuven, Belgium. jan.dequeker@med.kuleuven.ac.be
authors.forename: Jan
authors.initials: J
authors.lastname: Dequeker
authors.forename: Jeroen
authors.initials: J
authors.lastname: Aerssens
authors.forename: Frank P
authors.initials: FP
authors.lastname: Luyten
mesh_terms: D000375:Aging; D001842:Bone and Bones / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D010003:Osteoarthritis / Q000473:pathology* / Q000503:physiopathology*; D010024:Osteoporosis / Q000473:pathology* / Q000503:physiopathology*