Aspirin Use and Bone Health: Unpacking the Controversy

For decades, daily low-dose aspirin has been recommended to prevent the development of cardiovascular disease and reduce the risk for myocardial infarction or stroke in middle-aged and older adults. However, the benefits of daily aspirin use are now being questioned as research has revealed potential detriments of the prophylactic treatment, particularly among those at increased risk for falls, bleeding, and fractures.^1,2

Aspirin works as a cyclooxygenase (COX) inhibitor via suppression of prostaglandin through both the COX-1 and COX-2 pathways, resulting in anti-inflammatory effects.^3,4 This indirectly may impact bone health as low-grade, chronic inflammation has been found to correlate with increased bone loss and fracture risk. Therefore, aspirin use may decrease bone loss and fracture risk by reducing chronic inflammation.⁵

In addition, prostaglandins are involved in the bone remodeling cycle—either by promoting osteoblastic bone formation or by increasing osteoclastic bone resorption and bone loss.^3,4 Logically, given its multiple mechanisms of action on both the COX-1 and COX-2 pathways, aspirin use could either decrease bone density by inhibiting bone formation or promote bone formation and increase bone density by inhibiting bone resorption.⁴

While aspirin, ibuprofen, and naproxen all are nonselective nonsteroidal anti-inflammatory drugs (NSAIDs), some NSAIDs selectively inhibit only the COX-2 pathway, which, in turn, may decrease osteoclastic bone resorption and promote increased bone mineral density (BMD).⁶

These conflicting mechanisms of action of nonselective NSAIDs explain the diverse research findings from studies investigating the effect of NSAID use, including aspirin, on bone health.  

Lately, there has been a lot of debate about whether daily aspirin use is contraindicated or should be used with caution, on a case-by-case basis, in certain patient populations, including:

• older adults who may be at higher risk for life-threatening fractures due to falls,
• postmenopausal women at risk of developing osteoporosis,
• individuals healing from bone injuries, and
• patients with osteopenia or osteoporosis receiving treatment with bisphosphonates to preserve BMD.

Aspirin Use Among Older Adults

Research investigating the effect of daily aspirin use among older adults has reported conflicting results. While some studies have documented that daily low-dose aspirin use was correlated with increased BMD,⁷ others have suggested that daily low-dose aspirin intake did not significantly or effectively prevent fractures in this patient population.^8,9 In addition, a study reported an association between aspirin use and increased risk for falls leading to fractures in healthy, community-dwelling, older adults.⁸

Aspirin Use Among Postmenopausal Women

According to the Endocrine Society, approximately 1 in 10 women older than 60 years develop osteoporosis, resulting in decreased quality of life and morbidity.¹⁰ Postmenopausal women are at increased risk for primary osteoporosis due to naturally declining estrogen levels, usually developing within 10 to 15 years after menopause.¹¹

Daily aspirin use has shown an ability to increase BMD in some studies,⁷ so researchers have questioned whether daily aspirin use could affect BMD of postmenopausal women at risk for osteoporosis.

In a study, daily aspirin use did not contribute to decreased femoral or vertebral BMD among postmenopausal women.¹² Researchers observed that daily aspirin use was associated with between 2.3% and 5.8% increased BMD in the hip and spine. These findings suggested that daily aspirin consumption may exert modest beneficial effects on BMD in this patient subgroup.^12,13

However, fracture risk in this patient subgroup remained similar regardless of daily aspirin use. This indicated that increased BMD does not necessarily equate to decreased fracture risk.¹³

Effect of Aspirin on Fracture Healing

Because aspirin can potentially inhibit bone formation, concerns arose regarding the prolonged use of aspirin for analgesia while healing from a fracture or bony defect.

According to a recent literature review published in 2021, data from 6 randomized controlled trials demonstrated that risk for nonunion in healing fractures was higher among patients receiving treatment with NSAIDs for more than 4 weeks. However, patients with fractures with limited NSAID use of less than 2 weeks did not demonstrate increased risk for nonunion.¹⁴

Another review of the published literature echoed these findings, encouraging physicians treating patients with fractures or bony defects to administer COX-2 inhibitors or other NSAIDs for pain management only in the short-term to prevent delayed fracture healing.¹⁵

Effect of Aspirin on Bisphosphonate Use

A study published in the Journal of Bone and Mineral Research reported that NSAID use significantly increased risk for osteoporotic fractures in women aged 75 years and older during the 3-year study period (hazard ratio [HR], 1.27; 95% CI, 1.01-1.62; P =.039).¹⁶

In addition, women receiving treatment with the bisphosphonate clodronate concurrently with NSAIDs experienced greater bone loss in the femoral neck than those who received treatment with clodronate without NSAIDs (-3.06% vs -1.12% bone loss; P =.028).¹⁶ This observation suggests that use of NSAIDs may negate the positive effects of bisphosphonates on preserving BMD in certain patient populations.

Conclusion

Because aspirin is not a selective NSAID and affects various aspects of the bone remodeling process, special consideration must be given to certain patient groups, including older adults at risk for falling, postmenopausal women, individuals healing from bone injuries, and patients receiving bisphosphonates to preserve BMD.

While daily aspirin use may increase BMD in some individuals, it does not translate to decreased fracture risk. Prolonged aspirin or NSAID use may also negate the effect of bisphosphonates, delay fracture healing, and increase risk for falling among older adults.

Overall, clinicians should consider examining the risks and benefits of daily low-dose aspirin use on a case-by-case basis, assessing the individual’s bone health, risk for falling, cardiovascular disease risk factors that may require prophylaxis, and the need for long-term pain management.

This article originally appeared on Rheumatology Advisor