Subchondral bone in osteoarthritis

Grynpas, Marc D.; Alpert, Brian; Katz, Ian; Lieberman, Isador H.; Pritzker, Kenneth P.H.

doi:10.1007/bf02555898

Cited by 250 publications

(174 citation statements)

References 18 publications

Supporting

Mentioning

153

Contrasting

Unclassified

Order By: Relevance

“…(52) While there are some early signs of progress in understanding the molecular control of osteocyte differentiation from the osteoblast, with oncostatin M promoting differentiation along this pathway in tumor cells, (53) the regulation of osteocyte formation remains largely obscure in molecular terms. Whether mineralization is reduced in OA is a matter of debate because studies have reported that in hip OA, femoral head cancellous (5) and subchondral bone (54) is less mineralized, contrasting with iliac cortical bone, which is more highly mineralized in OA. (55) Boneformation rates are higher in subchondral bone in OA.…”

Section: Discussionmentioning

confidence: 99%

Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture

Power

Poole

Bezooijen

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

Remodeling imbalance in the elderly femoral neck can result in thin cortices and porosity predisposing to hip fracture. Hip osteoarthritis protects against intracapsular hip fracture. By secreting sclerostin, osteocytes may inhibit Wnt signaling and reduce bone formation by osteoblasts. We hypothesised that differences in osteocytic sclerostin expression might account for differences in osteonal boneformation activity between controls and subjects with hip fracture or hip osteoarthritis. Using specific antibody staining, we determined the osteocytic expression of sclerostin within osteons of the femoral neck cortex in bone removed from subjects undergoing surgery for hip osteoarthritis (hOA: 5 males, 5 females, 49 to 92 years of age) or hip fracture fixation (FNF: 5 males, 5 females, 73 to 87 years of age) and controls (C: 5 males, 6 females, 61 to 90 years of age). Sclerostin expression and distances of each osteocyte to the canal surface and cement line were assessed for all osteonal osteocytes in 636 unremodeled osteons chosen from fields ($0.5 mm in diameter) with at least one canal staining for alkaline phosphatase (ALP), a marker of bone formation. In adjacent sections, ALP staining was used to classify basic multicellular unit (BMUs) as quiescent or actively forming bone (ALP þ ). The areal densities of scl À and scl þ osteocytes (number of cells per unit area) in the BMU were inversely correlated and were strong determinants of ALP status in the BMU. In controls and hip fracture patients only, sclerostin-negative osteocytes were closer to osteonal surfaces than positively stained cells. Osteon maturity (progress to closure) was strongly associated with the proportion of osteonal osteocytes expressing sclerostin, and sclerostin expression was the chief determinant of ALP status. hOA patients had 18% fewer osteocytes per unit bone area than controls, fewer osteocytes expressed sclerostin on average than in controls, but wide variation was seen between subjects. Thus, in most hOA patients, there was increased osteonal ALP staining and reduced sclerostin staining of osteocytes. In FNF patients, newly forming osteons were similar in this respect to hOA osteons, but with closure, there was a much sharper reduction in ALP staining that was only partly accounted for by the increased proportions of osteonal osteocytes staining positive for sclerostin. There was no evidence for a greater effect on ALP expression by osteocytes near the osteonal canal. In line with data from blocking antibody experiments, osteonal sclerostin appears to be a strong determinant of whether osteoblasts actively produce bone. In hOA, reduced sclerostin expression likely mediates increased osteoblastic activity in the intracapsular cortex. In FNF, full osteonal closure is postponed, with increased porosity, in part because the proportion of osteocytes expressing sclerostin increases sharply with osteonal maturation. ß

show abstract

Section: Discussionmentioning

confidence: 99%

Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture

Power

Poole

Bezooijen

et al. 2010

Journal of Bone and Mineral Research

View full text Add to dashboard Cite

show abstract

“…The bone closest to the articular cartilage has the greatest effect on cartilage integrity, with variations in stiffness and BMD probably causing more damage to cartilage than any other parameters under normal conditions [27,28]. Although OA at a later stage demonstrates a thickening of subchondral bone, explants of the femoral heads of OA patients at autopsy revealed a pattern of low mineralisation compared with that of normal [29,30]. Hence, the apparent increase in bone density in OA may be because of an increase in material density, and not mineral density [31][32][33].…”

Section: Correlation Between In Vivo Findings In Animals and Human Oamentioning

confidence: 99%

“…As mentioned above, some studies have indicated that subchondral bone changes precede and may be responsible for the evolution of cartilage lesions [29,95,96]. Others have indicated that subchondral bone changes would only be secondary to cartilage degradation [97,98].…”

Section: Interaction Between Subchondral Bone and Cartilagementioning

confidence: 99%

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Tat

Lajeunesse

Pelletier

et al. 2010

Best Practice & Research Clinical Rheumatology

156

121

View full text Add to dashboard Cite

Over the past few decades, significant progress has been made with respect to new concepts about the pathogenesis of osteoarthritis (OA). This article summarises some of the knowledge we have today on the involvement of the subchondral bone in OA. It provides substantial evidence that changes in the metabolism of the subchondral bone are an integral part of the OA disease process and that these alterations are not merely secondary manifestations, but are part of a more active component of the disease. Thus, a strong rationale exists for therapeutic approaches that target subchondral bone resorption and/or formation, and data evaluating the drugs targeting bone remodelling raise the hope that new treatment options for OA may become available.

show abstract

“…Initial work by Radin and colleagues suggested that, as a consequence of thickening and repair of trabecular microfractures, the subchondral plate was stiffened and stress increases within the overlying cartilage combined with repeated impact loading led to deterioration of the cartilage (Radin et al, , 1973. Additional studies in humans and animal models have confirmed that there are density-related changes in the subchondral bone in individuals with osteoarthritis (Radin et al, 1970b;Radin and Rose, 1986;Brandt et al, 1991;Grynpas et al, 1991;Dedrick et al, 1993;Matsui et al, 1997;Hayami et al, 2004;Wang et al, 2005), but whether the subchondral changes precede or follow the osteoarthritis remains a matter of continuing debate (Burr and Radin, 2003;Wang et al, 2005).…”

mentioning

confidence: 99%

Knee Posture Predicted from Subchondral Apparent Density in the Distal Femur: An Experimental Validation

Polk

Blumenfeld

Ahluwalia

2008

The Anatomical Record

View full text Add to dashboard Cite

Spatial patterning in the apparent density of subchondral bone can be used to discriminate between species that differ in their joint loading conditions. This study provides an experimental test of two hypotheses that relate aspects of subchondral apparent density patterns to joint loading conditions. First, the region of maximum subchondral apparent density (RMD) will correspond to differences in joint posture at the time of peak locomotor loads; and second, differences in maximum density between individuals will correspond to differences in exercise level. These hypotheses were tested using three age-matched samples of juvenile sheep. Two groups of five sheep were exercised, at moderate walking speeds, twice daily for 45 days on a treadmill with either a 0% or 15% grade. The remaining sheep were not exercised. Sheep walking on the inclined treadmill used more flexed knee postures than those in the level walking group at the time of peak vertical ground reaction forces. Kinematic measurements of knee posture were compared with knee postures estimated from the spatial position of the RMD on the medial femoral condyle. Our results show that the difference in the position of the RMD between the incline and level walking groups corresponded to the difference in knee postures obtained kinematically; however, exercised and nonexercised sheep did not differ in the magnitude of apparent density. These results suggest that patterns of subchondral apparent density are good indicators of the experimental modifications in joint posture during locomotion and may, therefore, be used to investigate differences between species in habitual joint loading.

show abstract

Subchondral bone in osteoarthritis

Cited by 250 publications

References 18 publications

Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture

Sclerostin and the regulation of bone formation: Effects in hip osteoarthritis and femoral neck fracture

Targeting subchondral bone for treating osteoarthritis: what is the evidence?

Knee Posture Predicted from Subchondral Apparent Density in the Distal Femur: An Experimental Validation

Contact Info

Product

Resources

About