Bisphosphonates intake and its association with changes of periarticular bone area and three-dimensional shape: data from the Osteoarthritis Initiative (OAI)

Haj‐Mirzaian, Arya; Guermazi, Ali; Roemer, Frank W.; Bowes, M.A.; Conaghan, Philip G.; Demehri, Shadpour

doi:10.1016/j.joca.2018.01.005

Cited by 14 publications

(7 citation statements)

References 14 publications

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“…Furthermore, extensive sensitivity analyses showed conclusions were unchanged when accounting for potential residual confounding, healthy-user bias, or exposure misclassification. This study adds to previous research demonstrating protective effects of bisphosphonates for certain knee OA outcomes, including potential protection from joint space changes (33) and pain outcomes. (11) However, these studies did not take advantage of time-to-event data, instead using hypothesis testing methods to compare JSN (11,33) and pain outcomes.…”

Section: Discussionmentioning

confidence: 60%

“…This study adds to previous research demonstrating protective effects of bisphosphonates for certain knee OA outcomes, including potential protection from joint space changes (33) and pain outcomes. (11) However, these studies did not take advantage of time-to-event data, instead using hypothesis testing methods to compare JSN (11,33) and pain outcomes. (11) Previous work also did not investigate KL progression, which includes a number of osseous features such as osteophytosis and attrition that could reflect bone remodeling of the knee and which may be affected by bisphosphonate effects on subchondral bone.…”

Section: Discussionmentioning

confidence: 60%

“…Our results may partially elucidate why results differ between trials, observational studies, and meta-analyses (5,(11)(12)(13)(14)(15)(16)33) examining the benefit of bisphosphonates for various radiographic and symptomatic outcomes. Prior to examining effects, it is Weighted by stabilized and truncated (at the 5th and 95th percentile) inverse probability censor weights.…”

Section: Discussionmentioning

confidence: 86%

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Bisphosphonate Use Is Protective of Radiographic Knee Osteoarthritis Progression Among those With Low Disease Severity and Being Non-Overweight: Data From the Osteoarthritis Initiative

Hayes

Giannakeas

Wong

2020

Journal of Bone and Mineral Research

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Antiresorptive medications have been explored for treating knee osteoarthritis (OA); however, little data exist on the effects of today's more potent nitrogen‐containing oral bisphosphonates on radiographic disease‐progression in patients with varying disease‐severity, especially those who are not overweight. The primary objective of this cohort study was to determine if the use of bisphosphonates is protective against 2‐year radiographic‐progression of knee OA in Osteoarthritis Initiative (OAI) participants, stratified by baseline radiographic disease status. Secondary objectives were to examine effects in non‐overweight participants (body mass index [BMI] < 25 kg/m2) and cumulative bisphosphonate exposure effects. We identified female OAI participants aged ≥50 years and excluded those missing baseline radiograph readings, bisphosphonate use information, or all clinical questionnaire information at baseline. Participants reporting bisphosphonate use (69% alendronate) were propensity‐matched 1:1 to non–bisphosphonate users and followed until first radiographic knee OA progression (1‐unit increase in Kellgren and Lawrence [KL] grade) or data were censored (first missed visit or end of 2‐year follow‐up). Discrete‐time logistic regression models estimated hazard ratios (HRs) between bisphosphonate users versus nonusers, with an interaction term for baseline KL grade (KL <2 or KL ≥2). We identified 1977 eligible women (n = 346 bisphosphonate users). Propensity‐matched results indicated that bisphosphonate users with KL grade <2 were protected against progression (HRKL<2 0.53; 95% CI, 0.35 to 0.79), while bisphosphonate use was not associated with radiographic progression in those with KL grade ≥2 (HRKL≥2 1.06; 95% CI, 0.83 to 1.35). When restricting analyses to those with BMI <25 kg/m2, effects were strengthened (HRKL<2 0.49 [95% CI, 0.26 to 0.92]; HRKL≥2 0.69 [95% CI, 0.33 to 1.26]). Duration of bisphosphonate use had no effect on progression, though sample size was limited. Bisphosphonate therapy may be protective against radiographic knee OA progression in early‐stage patients, particularly those who are non‐overweight, but less so for those with more advanced disease or more weight‐bearing joint stress. © 2020 American Society for Bone and Mineral Research (ASBMR).

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Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 60%

Section: Discussionmentioning

confidence: 86%

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Bisphosphonate Use Is Protective of Radiographic Knee Osteoarthritis Progression Among those With Low Disease Severity and Being Non-Overweight: Data From the Osteoarthritis Initiative

Hayes

Giannakeas

Wong

2020

Journal of Bone and Mineral Research

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“…Subchondral bone includes trabecular bone and the subchondral bone plate, which is corticalized bone similar to that found in other locations. Human osteoarthritis studies using histological and imaging analyses showed that subchondral bone changes are generally characterized by increased bone sclerosis with thickening of the cortical plate, loss of subchondral trabecular rods with thickening of the remaining trabecular bone, alteration in subchondral bone 3-dimensional morphology (27), and formation of new bone at the joint margins (i.e., osteophytes) (28). These changes were detected in late-stage human osteoarthritis.…”

Section: Introductionmentioning

confidence: 99%

Senescent Preosteoclast Secretome Promotes Metabolic Syndrome-Associated Osteoarthritis through Cyclooxygenase 2

Wan

Liu

et al. 2022

Preprint

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Background: Metabolic syndrome–associated osteoarthritis (MetS-OA) is a distinct osteoarthritis phenotype defined by the coexistence of MetS or its individual components. Despite the high prevalence of MetS-OA, its pathogenic mechanisms are unclear. The aim of this study was to determine the role of cellular senescence in the development of MetS-OA. Methods: Analysis of the human osteoarthritis initiative (OAI) dataset was conducted to investigate the MRI subchondral bone features of MetS-human OA participants. Joint phenotype and senescent cells were evaluated in two MetS-OA mouse models: high-fat diet (HFD)-challenged mice and STR/Ort mice. In addition, the molecular mechanisms by which preosteoclasts become senescent as well as how the senescent preosteoclasts impair subchondral bone microenvironment were characterized using in vitro preosteoclast culture system. Results: Humans and mice with MetS are more likely to develop osteoarthritis-related subchondral bone alterations than those without MetS. MetS-OA mice exhibited a rapid increase in joint subchondral bone plate and trabecular thickness before articular cartilage degeneration. Subchondral preosteoclasts undergo senescence at the pre- or early-osteoarthritis stage and acquire a unique secretome to stimulate osteoblast differentiation and inhibit osteoclast differentiation. Antagonizing preosteoclast senescence markedly mitigates pathological subchondral alterations and osteoarthritis progression in MetS-OA mice. At the molecular level, preosteoclast secretome activates COX2-PGE2, resulting in stimulated differentiation of osteoblast progenitors for subchondral bone formation. Administration of a selective COX2 inhibitor attenuated subchondral bone alteration and osteoarthritis progression in MetS-OA mice. Longitudinal analyses of the human Osteoarthritis Initiative (OAI) cohort dataset also revealed that COX2 inhibitor use, relative to non-selective nonsteroidal anti-inflammatory drug use, is associated with less progression of osteoarthritis and subchondral bone marrow lesion worsening in participants with MetS-OA. Conclusions: Our findings suggest a central role of a senescent preosteoclast secretome-COX2/PGE2 axis in the pathogenesis of MetS-OA, in which selective COX2 inhibitors may have disease-modifying potential. Funding: This work was supported by the National Institutes of Health grant R01AG068226 and R01AG072090 to M.W., R01AR079620 to S.D., and P01AG066603 to X.C.

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“…Based on recent advances in understanding OA pathogenesis, several DMOAD candidates are currently under investigation. Based on evidence that subchondral bone may play a crucial role in OA progression, drugs such as bisphosphonates, calcitonin and strontium ranelate that can reduce bone resorption and increase bone formation are under consideration [166] [194] [195]. Inflammation and mechanical injury in OA leads to excessive activation of Wnt signaling, which increases transformation of mesenchymal stem cells (MSCs) to bone and induces MMP production, leading to cartilage degeneration.…”

Section: Osteoarthritismentioning

confidence: 99%

Cartilage diseases

2018

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Hyaline cartilages, fibrocartilages and elastic cartilages play multiple roles in the human body including bearing loads in articular joints and intervertebral discs, providing joint lubrication, forming the external ears and nose, supporting the trachea, and forming the long bones during development and growth. The structure and organization of cartilage's extracellular matrix (ECM) are the primary determinants of normal function. Most diseases involving cartilage lead to dramatic changes in the ECM which can govern disease progression (e.g., in osteoarthritis), cause the main symptoms of the disease (e.g., dwarfism caused by genetically inherited mutations) or occur as collateral damage in pathological processes occurring in other nearby tissues (e.g., osteochondritis dissecans and inflammatory arthropathies). Challenges associated with cartilage diseases include poor understanding of the etiology and pathogenesis, delayed diagnoses due to the aneural nature of the tissue and drug delivery challenges due to the avascular nature of adult cartilages. This narrative review provides an overview of the clinical and pathological features as well as current treatment options available for various cartilage diseases. Late breaking advances are also described in the quest for development and delivery of effective disease modifying drugs for cartilage diseases including osteoarthritis, the most common form of arthritis that affects hundreds of millions of people worldwide.

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Bisphosphonates intake and its association with changes of periarticular bone area and three-dimensional shape: data from the Osteoarthritis Initiative (OAI)

Abstract: Bisphosphonate intake was associated with a reduction in the odds (approaching but not achieving significance) of expansion periarticular bone area, specifically in the medial tibial sub-region.

Cited by 14 publications

References 14 publications

Bisphosphonate Use Is Protective of Radiographic Knee Osteoarthritis Progression Among those With Low Disease Severity and Being Non-Overweight: Data From the Osteoarthritis Initiative

Bisphosphonate Use Is Protective of Radiographic Knee Osteoarthritis Progression Among those With Low Disease Severity and Being Non-Overweight: Data From the Osteoarthritis Initiative

Senescent Preosteoclast Secretome Promotes Metabolic Syndrome-Associated Osteoarthritis through Cyclooxygenase 2

Cartilage diseases

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