The most common drugs used for pain and inflammation are the non-steroidal anti-inflammatory drugs (NSAIDs) like ibuprofen.  It is estimated that some 30 billion doses of these drugs are consumed each year in the U.S.  A growing body of research is suggesting that these drugs may actually increase the bone loss associated with osteoporosis. 

It is well established that NSAIDs “big brother”, prednisone clearly increases the risk of osteoporosis.  Ongoing use of prednisone for asthma or autoimmune disease such as rheumatoid arthritis results in secondary osteoporosis in up to 50% of subjects.  Prednisone both inhibits calcium absorption and increases activity in osteoclasts, the cells that remove bone in the disease. (1)

The suspicion that NSAIDs may cause increased bone loss in osteoporosis came from studies which examined the impact of these drugs on fracture healing.  A review of the data from the available human trials, it found that the risk of non-union or the failure of healing was increased 3.47 fold in using NSAIDs for the associated pain. (2)

The negative impact of NSAIDs on bone healing and fracture naturally led to the question of do these drugs increase osteoporosis risk and outcomes?  A study of 5212 women with osteoporosis looked at differences in treatment effect with a bisphosphonate, the first line drugs used to treat bone loss, in those also taking NASIDS compared to those not using these drugs.

The group of 1082 taking NSAIDs had a 27% increased risk of osteoporotic fracture compared to non-users. (3)  While the bisphosphonate decreased the fracture risk in women not taking NSAIDs, this benefit was negated in those using them.  The researchers concluded “The efficacy of the bisphosphonate, clodronate, to reduce fracture risk was largely negated in those receiving NSAIDs”.

The link between osteoporosis and NSAIDs relates to the impact of these drugs on the molecule prostaglandins E2 (PGE₂).  PGE₂ has different roles at different time points in injury and healing.  With tissue injury, inflammation is initiated to clean up the damaged tissue.  As that process proceeds, the role of PGE2 then reverses from one of removing damaged tissue to one of stimulating tissue rebuilding.

Looking at the top of the diagram the production of PGE2 depends on the COX-1 and COX-2 enzymes converting omega-6 fatty acids into the different prostaglandins.  While blocking the COX enzymes with NSAIDs relieves initial inflammation, it also will block the time delayed effect of stimulating tissue regeneration.

As a safe and effective alternative to NSAIDs, the natural products curcumin and resveratrol inhibit inflammatory symptoms equal to NSAIDs but also have tissue regenerative properties.  In a recent review of the studies looking at the comparative effect of curcumin and NSAIDs on degenerative arthritis of the knee.  Improvements in pain scores and function were equal in those taking curcumin and NSAIDs. (5)  Unlike the NSAIDs which impede healing and tissue regeneration, curcumin actually increased these. (6)

If there is a drawback to using herbs rather than NSAIDs for inflammation, it is that they don’t create the quick effect.  While a couple of ibuprofen may bring some relief in an hour, the herbs build the effect over a couple of weeks.  With chronic inflammation, the delay is minor compared to the advantages.

1. Kobza ao et al.  UNDERSTANDING AND MANAGING CORTICOSTEROID-INDUCED OSTEOPOROSIS. OPEN ACCESS RHEUMATOL. 2021 JUL 2;13:177-190.
2. Al farii et al.  THE EFFECT OF NSAIDS ON POSTFRACTURE BONE HEALING: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS. OTA INT. 2021 MAR 22;4(2):E092.
3. Zheng et al.  POTENTIAL ADVERSE EFFECT OF NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDS) ON BISPHOSPHONATE EFFICACY: AN EXPLORATORY POST HOC ANALYSIS FROM A RANDOMIZED CONTROLLED TRIAL OF CLODRONATE.  J BONE MINERAL RESEARCH, 2022;37(6): 1117-1124.
4. Cheng et al. ROLE OF PROSTAGLANDIN E2 IN TISSUE REPAIR AND REGENERATION. THERANOSTICS. 2021 AUG 13;11(18):8836-8854.
5. Hidayat et al.  EFFICACY OF CURCUMA LONGA IN RELIEVING PAIN SYMPTOMS OF KNEE OSTEOARTHRITIS PATIENTS: A SYSTEMATIC REVIEW AND METAANALYSIS OF CLINICAL TRIALS.  J RHEUM DIS 2025;32:17-29.
6. Barchitta et al.  NUTRITION AND WOUND HEALING: AN OVERVIEW FOCUSING ON THE BENEFICIAL EFFECTS OF CURCUMIN. INT J MOL SCI. 2019 MAR 5;20(5):1119.