Spironolactone for People Age 70 Years and Older With Osteoarthritic Knee Pain: A Proof‐of‐Concept Trial

Abstract

ObjectiveTo determine whether spironolactone could benefit older people with osteoarthritis (OA), based on a previous study showing that spironolactone improved quality of life.MethodsThis parallel‐group, randomized, placebo‐controlled, double‐blind trial randomized community‐dwelling people ages ≥70 years with symptomatic knee OA to 12 weeks of 25 mg daily oral spironolactone or matching placebo. The primary outcome was between‐group difference in change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale scores. Secondary outcomes included WOMAC stiffness and physical function subscores, EuroQol 5‐domain (EQ‐5D) 3L score, and mechanistic markers. Analysis was by intent to treat, using mixed‐model regression, adjusting for baseline values of test variables.ResultsA total of 421 people had eligibility assessed, and 86 were randomized. Mean ± SD age was 77 ± 5 years and 53 of 86 (62%) were women. Adherence to study medication was 99%, and all participants completed the 12‐week assessment. No significant improvement was seen in the WOMAC pain score (adjusted treatment effect 0.5 points [95% confidence interval (95% CI) − 0.3, 1.3]; P = 0.19). No improvement was seen in WOMAC stiffness score (0.2 points [95% CI −0.6, 1.1]; P = 0.58), WOMAC physical function score (0.0 points [95% CI −0.7, 0.8]; P = 0.98), or EQ‐5D 3L score (0.04 points [95% CI −0.04, 0.12]; P = 0.34). Cortisol, matrix metalloproteinase 3, and urinary C‐telopeptide of type II collagen were not significantly different between groups. More minor adverse events were noted in the spironolactone group (47 versus 32), but no increase in death or hospitalization was evident.ConclusionSpironolactone did not improve symptoms, physical function, or health‐related quality of life in older people with knee OA.

Effects of blood pressure and antihypertensive drugs on osteoarthritis: a mendelian randomized study

“…This improvement was demonstrated 5 month post-treatment, with about one-third of the Spironolactone group reporting pain and discomfort relief. Conversely, another proof-of-concept test involving 86 subjects based on this study found that taking Spironolactone does not significantly improve pain or quality of life among knee OA patients, whose average age surpassed 77 years old [ 27 ]. However, the study did indicate that taking 25 mg Spironolactone daily is highly safe for OA patients in this age group.…”

Pain mechanisms in the transgender individual: a review

“…Little is known about the impact of these drugs alone or in combination with estrogens—which is how they would typically be taken for gender transition—on chronic pain. Spironolactone in isolation has been reported to decrease inflammatory pain-related behavior in male mice ( 161 ) and neuropathic pain-related behavior in rats ( 162 ), but it did not alter fibromyalgia pain in women ( 163 ), or pain in human osteoarthritis patients of either sex ( 164 ). Research is needed to determine whether combined estrogens + anti-androgens are likely to affect chronic pain in preoperative vs. postoperative trans individuals.…”