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Bisphosphonates for orthopaedic patients: More than just osteoporosis treatment

Dr Yoon Kam Hon
11 Jun 2019
Osteoarthritis (OA) affects 240 million people globally and in Asia, 35 percent suffer from this crippling disease. In a recent symposium held in conjunction with the Singapore Orthopaedic Association 52nd Annual General Meeting, Dr Yoon Kam Hon, Consultant Rheumatologist, El Shaddai Arthritis and Rheumatism Specialist Medical Centre, Singapore, discussed the role of bisphosphonates beyond OA and fracture prevention, including the benefits of the newest innovative buffered alendronate (Binosto®) in orthopaedic patients.

Ageing is characterized by elevated levels of blood inflammatory markers, a phenomenon called “inflamm-ageing” [Int J Mol Sci 2019;20:614], and carries with it an increased susceptibility to comorbidity, disability, and frailty, including OA. “OA is one of the leading causes of disability in Asia,” said Yoon. “It is a heterogeneous and multifaceted disease with multiple causes, molecular endotypes, and clinical subtypes.”

Patients may present with synovitis-driven inflammatory phenotype which can be local and systemic. Others may have subchondral bone remodelling, metabolic, subchondoral bone, or injury-driven phenotype. Still others present with sarcopenic muscle or senescent-age related phenotype. [Curr Opin Rheumatol 2019;31:80-89]

Bisphosphonates in osteoporosis
“Often, patients with osteoporosis also present with OA, increasing in frequency with advancing age and postmenopause,” said Yoon. Oral bisphosphonates are the mainstay of treatment for postmenopausal women with osteoporosis. [J Clin Endocrinol Metab 2019;104:1595-1622)

Alendronate is the most widely used bisphosphonate worldwide for osteoporosis. The efficacy of alendronate for fracture risk reduction in osteoporosis was demonstrated in the Fracture Intervention Trial (FIT). Reductions in the risks of hip, clinical vertebral, and wrist fractures were 53%, 45%, and 30%, respectively, with alendronate. [J Clin Endocrinol Metab 2000;85:4118-4124]

In a meta-analysis of oral bisphosphonates, treatment with alendronate showed the greatest reduction in vertebral, hip, and nonvertebral fracture risks compared with risedronate and ibandronate. [J Clin Endocrinol Metab 2019;104:1623-1630; J Clin Endocrinol Metab 2019;104:1595-1622]

Aside from alendronate’s antifracture efficacy in osteoporosis, it is also supported by good evidence demonstrating benefits for OA,” said Yoon.

Bisphosphonates in OA
A meta-analysis of randomized controlled trials conducted by Xing et al involving 15 eligible studies and 3,566 participants showed that treatment with bisphosphonates improved pain, stiffness, and joint function (p<0.00001; p=0.0005 and p<0.00001, respectively) as measured on an arthritis index scale, and accelerated functional recovery of OA patients. [Springerplus 2016;5:1704]

Bone remodelling as a therapeutic target in OA is also important. Repair of the microdamage to the bone matrix in OA is part of the current understanding of the multifaceted treatment of OA, said Yoon.

A secondary analysis of data from FIT showed alendronate was associated with less spinal osteophytes and decreased disc-space narrowing. [Ann Rheum Dis 2008;67:1427-30]

“Several preclinical studies and observational clinical studies suggest that bisphosphonates have a role in altering the pathological processes of knee OA,” said Yoon. (Figure 1)

Binosoto Fig01

Bisphosphonates in joint replacement surgery
Bisphosphonate use was also associated with a significantly lower risk of total knee arthroplasty (TKA; adjusted hazard ratio [adjHR], 0.76; p<0.001) in a nationwide cohort study in Taiwan involving patients with osteoporosis and knee OA.  An even greater effect was seen in patients with high adherence (medication possession ratio, ≥80%) and longer treatment duration (≥24 months). Use of pain medication was also lower among bisphosphonate users than nonusers (p<0.001) over 5 years of follow-up. [J Bone Joint Surg Am 2017;99:938-946]

Similarly, a UK study assessing the effects of bisphosphonates on knee replacement surgery in older women with OA demonstrated that bisphosphonate users had a 26 percent lower risk of knee replacement surgery vs nonusers, suggesting a potential beneficial effect of bisphosphonates on knee OA. [Ann Rheum Dis 2018;77:92-97]

“Given these results, the use of bisphosphonates is something we should advocate to our patients, particularly those who are not fit or eligible for TKA or total knee replacement [TKR] surgery but would require pain relief,” said Yoon.

After TKR, patients have a higher risk of lower bone mineral density (BMD), predisposing them to increased risk of fractures. Bisphosphonate treatment for 1 year has been shown to prevent early reduction of hip BMD after TKR in a Korean study. [J Bone Metab 2013;20:105-109]

“Bisphosphonates reduce periprosthetic bone loss, improve hip BMD, and reduce the risk of implant revision after TKR (Figure 2). I would therefore advise the use of bisphosphonates post-TKR to prevent hip fractures in elderly patients with severe knee OA,” said Yoon.

Binosoto Fig02

Binosto®: Innovative buffered solution of alendronate
Binosto®, the newest innovative buffered effervescent solution of alendronate, has proven efficacy of alendronate tablet in fracture risk reduction. Unlike conventional oral bisphosphonates, Binosto® provides enhanced gastric tolerability due to its buffered formulation, keeping the gastric pH to >5, thus effectively reducing stomach acidity. Persistence to treatment was higher with Binosto® at 6 and 12 months compared with oral alendronate tablets (Figure 3). [Osteoporos Int 2018;29(1):853(Suppl 1]

Binosoto Fig03

“My patients like the new buffered solution of alendronate better because it has less upper gastrointestinal [GI] effects, which allows them to stay on treatment,” said Yoon. The use of Binosto® also makes it possible to reduce reliance on PPIs, which are often given with conventional bisphosphonates.

Conclusion
The incidence of “inflamm-ageing” is increasing worldwide; Singapore is not immune to this phenomenon. The recognition of OA phenotypes, clinical subtypes, and the molecular taxonomy about different OA subgroups allow clinicians to provide targeted therapy to different OA patients.  New emerging OA disease-modifying treatments are available. There is a role for bisphosphonates in OA therapy. Hence, orthopaedic surgeons should advocate bisphosphonate therapy in OA patients with osteoporosis and post TKA/TKR patients, said Yoon.
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Most Read Articles
09 Jul 2019
Patients who had undergone aortic valve replacement (AVR) have shorter life expectancy than the general population, a study has found. Apart from being substantial, this loss in life expectancy increases with younger age.
6 days ago
The consumption of red and processed meats does not seem to affect the likelihood of symptom relapse among Crohn’s disease (CD) patients in relapse, reports a recent study.
Pearl Toh, 12 Jul 2019
Restarting antiplatelet therapy in survivors of intracranial haemorrhage (ICH)-related stroke is safe without raising their risk of a recurrent ICH, contrary to the commonly perceived risk of a recurrence with an antithrombotic drug, the RESTART* trial has shown.
Elaine Soliven, 4 days ago

Disease-free survival (DFS) at 3 years was comparable between patients with locally advanced gastric cancer who underwent laparoscopic distal gastrectomy and open distal gastrectomy, pointing to the noninferiority of the laparoscopic procedure to the open one, according to the CLASS-01* study.