A 2 yr longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients

Buckland‐Wright, J. C.; Messent, E. A.; Bingham, Clifton O.; Ward, Rupert; Tonkin, C.

doi:10.1093/rheumatology/kel213

Cited by 112 publications

(95 citation statements)

References 50 publications

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“…We found that alendronate significantly, and risedronate to some degree, reduced trabecular bone volume loss in the medial femoral compartment compared with untreated rats early after a knee triad injury. These findings were consistent with those of previous studies examining posttraumatic OA in several other animal models (9,31) and were also supported by the results of investigations of risedronate in later-stage human OA (26).…”

Section: Discussionsupporting

confidence: 92%

“…The analgesic acetaminophen is the first-line therapy indicated for OA treatment and is used for pain management, with no known disease-modifying benefits. Several bisphosphonate drugs have previously been shown to have disease-modifying treatment outcomes in OA in animal models (23)(24)(25) and humans (26)(27)(28). However, those studies had contradictory results regarding the disease-modifying efficacy of bisphosphonate drugs, particularly since most studies in humans involved patients with end-stage OA, rather than individuals at an earlier stage of OA pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

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In vivo microfocal computed tomography and micro–magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat

Jones

Tran

et al. 2010

Arthritis & Rheumatism

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Objective. To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA).Methods. We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro-magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam.Results. Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion-like stimulus. In contrast, meloxicamtreated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury.Conclusion. Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion-like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

In vivo microfocal computed tomography and micro–magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat

Jones

Tran

et al. 2010

Arthritis & Rheumatism

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“…These results were consistent with those of earlier published studies [8,19] . Similar to previous studies [19,29] , the current study showed that bisphosphonates demonstrated a protective effect on cartilage and bone changes related to OA in a dose-dependent manner. To better elucidate the timedependent effects of the therapy, the higher dose was chosen.…”

Section: Discussionsupporting

confidence: 89%

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Mao

et al. 2012

Acta Pharmacol Sin

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Aim: To investigate whether the stage of osteoarthritis (OA) progression influenced the efficacy of the third-generation bisphosphonate zoledronic acid in a rat medial meniscal tear model. Methods: Medial meniscal tear (MMT) was surgically induced in adult male Sprague Dawley rats. Zoledronic acid (ZOL, 100 μg/kg, sc, twice a week) was administered starting immediately, early (from 4 weeks) or late (from 8 weeks) after OA induction. The degeneration of articular cartilage was evaluated with toluidine blue O staining. Subchondral bone remodeling was evaluated with X-ray micro-CT scanning. Joint pain was measured with respect to weight-bearing asymmetry. Calcitonin gene-related peptide (CGRP) expression in dorsal root ganglia (DRGs) was examined using immunofluorescence analysis. The afferent neurons in DRGs innervating the joint were identified by retrograde labeling with fluorogold. Results: Progressive cartilage loss was observed during 12 weeks after OA induction. Subchondral bone remodeling manifested as increased bone resorption at early stage (4 weeks), but as increased bone accretion at advanced stages (8 weeks). Immediately and early ZOL administration significantly improved subchondral microstructural parameters, attenuated cartilage degeneration, reduced weight-bearing asymmetry and CGRP expression, whereas the late ZOL administration had no significant effects. Conclusion: The stage of OA progression influences the efficacy of ZOL in treating joint degeneration and pain. To obtain the maximum efficacy, bisphosphonate treatment should be initiated in rat with early stages of OA pathogenesis.

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“…Treatment with risedronate reduced the level of CTX-II in patients with knee OA over two years, although no effect on signs or symptoms or alterations of the progression of OA was observed [17]. A longitudinal radiographic study examining the effects of risedronate at 15 mg/day or 50 mg/week showed that preservation of the structural integrity of the subchondral bone in knee OA in patients with marked cartilage loss [39]. These data suggested that the results were attributed to high doses of bisphosphonates as well as their repeated administration, which might contribute to enhanced bone accretion and formation, leading to protection of articular cartilage.…”

Section: Discussionmentioning

confidence: 99%

Changes in Serum Levels of Cartilage Oligomeric Matrix Protein after Estrogen and Alendronate Therapy in Postmenopausal Women

Seo

Yang²,

Lim³

et al. 2012

Gynecol Obstet Invest

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Background: Cartilage oligomeric matrix protein (COMP) is a biomarker for joint destruction and its serum levels are used for assessing therapeutic efficacy. This study aims to compare changes in serum COMP levels in postmenopausal women with osteopenia/osteoporosis receiving estrogen and alendronate. Methods: A total of 62 postmenopausal women diagnosed with osteopenia or osteoporosis were treated with either estrogen (17β-estradiol 1 mg, n = 30) or bisphosphonate (alendronate 5 mg, n = 32) for 6 months. The controls were healthy postmenopausal women (n = 30). Serum COMP and osteocalcin levels were measured at baseline and after 6 months of treatment. Results: Estrogen decreased levels of COMP at 6 months compared to baseline levels (–8.35 ± 19.38%), whereas the bisphosphonate and control groups resulted in no significant changes (–5.50 ± 18.69 and –1.49 ± 25.34%, respectively). Concentrations of osteocalcin decreased significantly in both treatment groups (estrogen –25.60 ± 24.42% and alendronate –13.76 ± 23.89%, respectively). There was a significant positive correlation between changes after 6 months in COMP and osteocalcin (R = 0.48, p = 0.002). Conclusions: Postmenopausal women treated with estrogen showed significantly decreased levels of COMP after 6 months. Estrogen might provide a further treatment modality in the prevention of joint destruction.

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A 2 yr longitudinal radiographic study examining the effect of a bisphosphonate (risedronate) upon subchondral bone loss in osteoarthritic knee patients

Cited by 112 publications

References 50 publications

In vivo microfocal computed tomography and micro–magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat

In vivo microfocal computed tomography and micro–magnetic resonance imaging evaluation of antiresorptive and antiinflammatory drugs as preventive treatments of osteoarthritis in the rat

Efficacy of zoledronic acid in treatment of teoarthritis is dependent on the disease progression stage in rat medial meniscal tear model

Changes in Serum Levels of Cartilage Oligomeric Matrix Protein after Estrogen and Alendronate Therapy in Postmenopausal Women

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