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Updated: May 23, 2026
Software-Assisted Quantitative Measurement of Osteoarthritic Subchondral Bone Thickness
Published on: March 18, 2022
Targeting bone alleviates osteoarthritis in osteopenic mice and modulates cartilage catabolism
Thomas Funck-Brentano1, Hilène Lin, Eric Hay
1INSERM U606, Centre Viggo Petersen and Université Paris-Diderot Paris 7, Hôpital Lariboisière, Paris, France.
Objective:
Subchondral bone modifications occur early in the development of osteoarthritis (OA). The level of bone resorption might impact cartilage remodeling. We therefore assessed the in vivo and in vitro effects of targeting bone resorption in OA and cartilage metabolism.
Methods:
OA was induced by meniscectomy (MNX) in ovariectomized osteopenic mice (OP) treated with estradiol (E2), pamidronate (PAM), or phosphate buffered saline (PBS) for 6 weeks. We assessed the subchondral bone and cartilage structure and the expression of cartilage matrix proteases. To assess the involvement of bone soluble factors in cartilage metabolism, supernatant of human bone explants pre-treated with E2 or PAM were transferred to cartilage explants to assess proteoglycan release and aggrecan cleavage. OPG/RANKL mRNA expression was assessed in bone explants by real-time quantitative PCR. The role of osteoprotegerin (OPG) in the bone-cartilage crosstalk was tested using an OPG neutralizing antibody.
Results:
Bone mineral density of OP mice and osteoclast number were restored by E2 and PAM (p<0.05). In OP mice, E2 and PAM decreased ADAMTS-4 and -5 expression, while only PAM markedly reduced OA compared to PBS (2.0±0.63 vs 5.2±0.95; p<0.05). OPG/RANKL mRNA was increased in human bone explants treated with both drugs (2.2-3.7-fold). Moreover, supernatants from bone explants cultured with E2 or PAM reduced aggrecan cleavage and cartilage proteoglycan release (73±8.0% and 80±22% of control, respectively, p<0.05). This effect was reversed with osteoprotegerin blockade.
Conclusion:
The inhibition of bone resorption by pamidronate in osteopenic mice alleviates the histological OA score with a reduction in the expression of aggrecanases. Bone soluble factors, such as osteoprotegerin, impact the cartilage response to catabolic factors. This study further highlights the importance of subchondral bone in the regulation of joint cartilage damage in OA.
Insights
Targeting bone resorption with pamidronate reduced osteoarthritis progression in mice by decreasing aggrecanase expression. Bone-derived factors like osteoprotegerin (OPG) mediate this protective effect on cartilage, highlighting subchondral bone
Area of Science:
- Orthopedics and Sports Medicine
- Rheumatology
- Cell Biology
Background:
- Subchondral bone changes are early indicators in osteoarthritis (OA) development.
- Bone resorption levels may influence cartilage remodeling processes in OA.
- Understanding the bone-cartilage crosstalk is crucial for OA pathogenesis.
Purpose of the Study:
- To investigate the effects of inhibiting bone resorption on osteoarthritis and cartilage metabolism.
- To assess the role of bone-derived soluble factors in regulating cartilage matrix degradation.
- To explore the impact of pamidronate and estradiol on subchondral bone and cartilage in an OA mouse model.
Main Methods:
- Osteoarthritis was induced in osteopenic mice via meniscectomy and treated with estradiol, pamidronate, or placebo.
- Subchondral bone and cartilage were analyzed histologically, alongside cartilage matrix protease expression.
- Human bone explant supernatants were used to assess cartilage proteoglycan release and aggrecan cleavage, with osteoprotegerin (OPG) blockade as a control.
Main Results:
- Pamidronate and estradiol treatments restored bone mineral density and reduced osteoclast numbers in osteopenic mice.
- Both agents decreased ADAMTS-4 and -5 expression, with pamidronate significantly reducing OA histological scores.
- Supernatants from treated bone explants inhibited cartilage aggrecan cleavage and proteoglycan release, an effect reversed by OPG blockade.
Conclusions:
- Inhibition of bone resorption, particularly with pamidronate, ameliorates OA in osteopenic mice by reducing aggrecanase expression.
- Bone-derived factors, including osteoprotegerin, play a significant role in the cartilage response to catabolic stimuli.
- This study underscores the critical involvement of subchondral bone in regulating joint cartilage damage in osteoarthritis.
