A six‐month randomized, controlled, double‐blind, dose‐response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug–refractory ankylosing spondylitis: Comment on the article by Maksymowych et al

Singh, Ranju; Menon, Yamini; Cuchacovich, Raquel; Espinoza, Luis R.

doi:10.1002/art.10717

Cited by 3 publications

(4 citation statements)

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“…58 In addition, aminobisphosphonates also show immunomodulatory and anti-inflammatory activity by interacting with proinflammatory cytokines, such as interleukin (IL)-1, the tumour necrosis factor and IL-6, and therefore inhibiting the antigen-presenting capacity of macrophages. [39][40][41][42] What this different mode of action implicates for the clinical potential in the treatment of HO is unknown. Thus, the new generation of bisphosphonates may produce less osteomalacia but theoretically may also have a lower potential of inhibiting HO.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, recent studies and case reports support its efficacy in different inflammatory, dysmorphogenic bone disease such as diabetic neuropathy (Charcot), reflex sympathetic dystrophy (M Sudeck), ankylosing spondylitis, or the SAPHO syndrome (synovitis, acne, pustulosis, hyperostosis and osteitis). [39][40][41][42][43]61,62 In these inflammatory syndromes of largely unknown cause and pathophysiology, amino-bisphosphonates are administered not only because of their antiosteoclastic effect, but rather for their immunomodulatory and antiinflammatory properties. If bisphosphonate therapy has been suggested to control bone metabolism activity in these multiple destructive inflammatory bone conditions, it is reasonable to believe that it may have a role in controlling osteoblast and osteoclastic activity in the acute inflammatory phase of HO.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, we speculated that amino-bisphosphonates could be administered not only because of their antiosteoclastic effect, but also for their immunomodulatory and anti-inflammatory properties. [39][40][41][42][43] Only single case reports have been published for the treatment with the more potent new generation of amino-bisphosphonates. 44 Herein we report our observational experience using the aminobisphosphonate Pamidronate in five consecutive patients with established HO.…”

Section: Introductionmentioning

confidence: 99%

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Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases

et al. 2005

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Study design: Retrospective, observational study in five consecutive cases. Objectives: The management of heterotopic ossification (HO), a frequent complication after spinal cord injury (SCI) and after orthopaedic surgery, is a therapeutic challenge with high recurrence rates of over 50%. Conflicting data were reported for Etidronate. The use of the more potent new generation of amino-bisphosphonates has been put forward in different inflammatory, dysmorphogenic bone disease. In order to try and halt the underlying dysfunctional bone metabolism we have studied the action of pamidronate in five consecutive high-risk patients with established HO of different etiology undergoing surgical removal. Setting: University Hospital of Basel, Switzerland, Division of Endocrinology, Diabetology and Clinical Nutrition and the Department of Orthopedic Surgery. Methods: In all five patients, ranging from 47 to 68 years of age, we used continuous pamidronate infusions perioperatively at a dosage of 120 mg in the first 12 h and subsequent reduction to 75-60-30-15 mg/12 h over a period of 10-14 days. Results: None of these patients showed clinical, radiographical and laboratory signs of HO recurrence or new forming HO in the follow-up 5-54 month after surgery. Potential side effects of high-dose bisphosphonate therapy such as osteoporosis and osteomalacia were not reported in any case. Conclusion: We postulate that pamidronate might have pronounced beneficial effects in highrisk patients with established HO undergoing excision surgery. Since the therapeutic window of amino-bisphosphonates has not yet been defined and the minimal necessary doses for preventing new HO are unknown, further studies are encouraged to confirm our findings and to identify the necessary dosage and duration of treatment and to pinpoint, which patients will benefit most from this treatment.Spinal Cord (2005) 43, 604-610.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases

et al. 2005

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“…26 AS patients treated with bisphosphonate achieve similar reductions in disease activity, which take the BASDAI and other clinical index as efficacy measure, compared with anti-inflammatory therapy and benefits to bone mineral density. 27 Treatment with bisphosphonates either improves the clinical index or ameliorated radiological progression in AS patients, [28][29][30][31] regardless of whether a short-term 28 or intermittent treatment was adopted. 29 Therefore, bony formation in AS not only originates from enthesitis; osteoclasts also play an important role in structural disease progression although the underlying mechanism has yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Chondrogenesis mediates progression of ankylosing spondylitis through heterotopic ossification

Zhang

Zhu

et al. 2021

Bone Res

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Ankylosing spondylitis (AS) is chronic inflammatory arthritis with a progressive fusion of axial joints. Anti-inflammatory treatments such as anti-TNF-α antibody therapy suppress inflammation but do not effectively halt the progression of spine fusion in AS patients. Here we report that the autoimmune inflammation of AS generates a microenvironment that promotes chondrogenesis in spine ligaments as the process of spine fusion. Chondrocyte differentiation was observed in the ligaments of patients with early-stage AS, and cartilage formation was followed by calcification. Moreover, a large number of giant osteoclasts were found in the inflammatory environment of ligaments and on bony surfaces of calcified cartilage. Resorption activity by these giant osteoclasts generated marrow with high levels of active TGF-β, which induced new bone formation in the ligaments. Notably, no Osterix+ osteoprogenitors were found in osteoclast resorption areas, indicating uncoupled bone resorption and formation. Even at the late and maturation stages, the uncoupled osteoclast resorption in bony interspinous ligament activates TGF-β to induce the progression of ossification in AS patients. Osteoclast resorption of calcified cartilage-initiated ossification in the progression of AS is a similar pathologic process of acquired heterotopic ossification (HO). Our finding of cartilage formation in the ligaments of AS patients revealed that the pathogenesis of spinal fusion is a process of HO and explained why anti-inflammatory treatments do not slow ankylosing once there is new bone formation in spinal soft tissues. Thus, inhibition of HO formation, such as osteoclast activity, cartilage formation, or TGF-β activity could be a potential therapy for AS.

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Pamidronate - a promising new candidate for the management of spondyloarthropathy

Akerkar¹,

Ls²

2005

Indian J Med Sci

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Bisphosphonate group of agents are known for their anti-bone resorptive properties. However, recently their anti-inflammatory and anti-arthritis properties have come to light. Clinical trials of their use in spondyloarthropathy are showing promising results, especially in patients with shorter disease duration. The adverse event profile is mainly limited to postinfusion arthralgia, myalgia and fever. The concept of pamidronate in spondyloarthropathy management should be evaluated further in light of these clinical studies and could have a major impact on our resource-restricted setting.

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A six‐month randomized, controlled, double‐blind, dose‐response comparison of intravenous pamidronate (60 mg versus 10 mg) in the treatment of nonsteroidal antiinflammatory drug–refractory ankylosing spondylitis: Comment on the article by Maksymowych et al

Cited by 3 publications

References 6 publications

Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases

Amino-bisphosphonates in heterotopic ossification: first experience in five consecutive cases

Chondrogenesis mediates progression of ankylosing spondylitis through heterotopic ossification

Pamidronate - a promising new candidate for the management of spondyloarthropathy

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