Crestor Bone Health and Density Impact: What the Evidence Shows

What does rosuvastatin's own trial data cover?

JUPITER, the main rosuvastatin outcomes trial, randomized 17,802 apparently healthy men and women with LDL cholesterol below 130 mg/dL and high-sensitivity C-reactive protein levels of at least 2.0 mg/L to rosuvastatin 20 mg daily or placebo [5]. It stopped at a median of 1.9 years: LDL-C fell 50%, hsCRP fell 37%, and the primary cardiovascular endpoint fell from 1.36 to 0.77 per 100 person-years (HR 0.56, 95% CI 0.46 to 0.69) [5]. The trial was built around cardiovascular events, and bone density or fracture was not its primary endpoint [5].

What statin-class studies show for bone density

A 2017 meta-analysis included 33 studies, 23 observational and 10 randomized controlled trials, covering 314,473 people taking statins and 1,349,192 controls [2]. Statin use was associated with higher bone mineral density at the lumbar spine (standardized mean difference 0.20, 95% CI 0.07 to 0.32) and total hip (0.18, 95% CI 0.00 to 0.36, so the lower bound touches zero), and with higher osteocalcin, a bone formation marker [2]. The same analysis found no positive effect on femoral neck density, vertebral fractures or upper-limb fractures, and the effect in women was small or not statistically significant [2].

An earlier meta-analysis of 21 studies, mostly observational, found modest but significant hip effects (effect size 0.21 at the total hip and 0.20 at the femoral neck across 16 analyzable studies and about 2,971 people on statins) [6]. In that analysis the hip effect came almost entirely from the lipophilic statins simvastatin and lovastatin [6].

Do statins reduce fractures?

Observational data point one way. In a nested case-control study from the UK General Practice Research Database, 3,940 people with a fracture were compared with 23,379 matched controls; current statin use was associated with lower odds of fracture (adjusted OR 0.55, 95% CI 0.44 to 0.69) than no lipid-lowering drug [3].

Randomized trial data do not show the same benefit. Bauer and colleagues analyzed four large prospective studies and added a cumulative meta-analysis: the observational studies gave a hip fracture odds ratio of 0.43 (95% CI 0.25 to 0.75), while the clinical trials gave 0.87 (95% CI 0.48 to 1.58) for hip fracture and 1.02 (95% CI 0.83 to 1.26) for nonspine fracture [4].

Why statins were expected to help bone

Statins block HMG-CoA reductase, the rate-limiting enzyme in cholesterol synthesis [1]. That pathway also produces isoprenoids that affect osteoclast activity, an effect amino-bisphosphonates share [6]. In 1999, Mundy and colleagues reported in Science that statins increased bone morphogenetic protein-2 gene expression in bone cells, that lovastatin and simvastatin increased bone formation when injected over the calvaria of mice, and that they raised cancellous bone volume when given orally to rats [7]. A 2006 review pointed to the obstacle: statins are highly liver-specific and have low oral bioavailability, so whether enough drug reaches the bone microenvironment is uncertain [8].

Does rosuvastatin cause muscle or joint pain?

Muscle aching is the symptom the label addresses most directly. In pooled placebo-controlled trials of up to 12 weeks, myalgia was reported by 2.8% of people on Crestor 5 to 40 mg and 1.3% on placebo; in METEOR (40 mg, mean 1.7 years) it was 12.7% versus 12.1%, and in JUPITER 7.6% versus 6.6% [1]. Arthralgia was also reported more often than on placebo: 10.1% versus 7.1% in METEOR and 3.8% versus 3.2% in JUPITER [1]. The label's muscle warning covers myopathy and rhabdomyolysis, with risk factors including age 65 or older, renal impairment, uncontrolled hypothyroidism, interacting drugs and higher doses; myopathy risk is greater at 40 mg than at lower doses [1].