Orthopedic Surgery

Medications and Injections: Weighing Risks and Benefits

At a Glance

For osteoarthritis pain, treatment should match your health risks and goals. Anti-inflammatory creams may limit whole-body exposure, while pills and injections can affect the stomach, heart, kidneys, blood sugar, or surgery timing; PRP and stem cells are not routinely recommended.

When lifestyle changes like exercise and weight management aren’t enough to manage osteoarthritis (OA) pain, medications and injections can provide additional relief. However, these treatments are not “one size fits all.” Current medical guidelines emphasize a shared decision-making approach, where you and your doctor weigh the potential benefits against your personal health risks, particularly your kidney, heart, and stomach health ^[1]^[2].

Topical and Oral Medications

Topical NSAIDs: Creams or gels containing non-steroidal anti-inflammatory drugs (like diclofenac) are strongly recommended for knee OA and recommended for hand OA ^[1]^[2]. Because they are applied directly to the skin, they provide relief with significantly lower “systemic exposure” than pills. However, absorption and adverse effects are not zero—they can cause skin reactions, and you should not combine them with oral NSAIDs without a doctor’s advice. They are also less effective for deep joints like the hip ^[3]^[4].
Oral NSAIDs: Pills like ibuprofen or naproxen are effective but carry more significant risks. They should be used at the lowest effective dose for the shortest time possible ^[5]. Your doctor must carefully evaluate interactions with other medicines (like anticoagulants, ACE inhibitors, or diuretics) and your risk for:
- Gastrointestinal (GI) Issues: Risk of stomach ulcers or bleeding. For those at higher risk, a proton-pump inhibitor (PPI) is sometimes selectively prescribed alongside an NSAID to protect the stomach ^[6]^[7].
- Cardiovascular Risks: Oral NSAIDs can raise blood pressure and increase the risk of heart events ^[4]^[6].
- Kidney Health: NSAIDs can decrease blood flow to the kidneys, which is a particular danger for people who are dehydrated, older adults, or those with chronic kidney disease (CKD) ^[4].
Acetaminophen: Once considered the first-line treatment, its average benefit for OA is often quite small, and guidelines frequently offer only conditional recommendations ^[1]^[2]. Explicit warnings apply: avoid exceeding the maximum daily dose, do not mix with alcohol, use caution with liver disease, and be very careful not to accidentally “stack” it with other over-the-counter cold/flu medications that also contain acetaminophen.
Duloxetine: Originally developed for depression, this is sometimes conditionally recommended for OA because it helps change how the nervous system processes pain ^[1]^[5]. Common adverse effects include nausea and fatigue, and it has important interactions with other medications.

Joint Injections: Steroids and Beyond

Injections deliver medication directly into the joint environment. Important safety note: A joint that is acutely hot, red, or suspected to be infected must be assessed by a doctor before any injection is given.

Corticosteroids: “Steroid shots” can provide significant short-term pain relief (often lasting a few weeks to a few months) ^[8]^[9]. There is no universally safe maximum number of injections; repeated injections at short intervals have raised concerns about accelerated cartilage loss ^[10]. Injections can also cause transient spikes in blood sugar (hyperglycemia), which is critical if you have diabetes.
- Surgery Note: If you are planning a joint replacement, surgeons generally require a minimum waiting period (often 3 to 4 months) after a steroid injection to reduce the risk of post-surgical infection. Inform your surgical team of your exact injection dates ^[11]^[12].
Hyaluronic Acid (HA): Often called “gel shots.” Evidence for HA is mixed; while some patients find relief, many major guidelines do not strongly recommend it because the benefit over a placebo is often inconsistent ^[13]^[14].
Platelet-Rich Plasma (PRP) and Stem Cells: These “regenerative” treatments are not recommended by major guidelines like ACR or OARSI for routine OA care ^[15]^[16]. Current research has not proven that they regrow cartilage, and they are typically expensive out-of-pocket costs ^[17]^[18].

A Note on Opioids

Current guidelines strongly advise against routine opioid use (like oxycodone) for long-term OA management ^[2]. Medications like tramadol may be considered in selected patients when other treatments are ineffective or contraindicated ^[1]. However, any opioid use requires careful discussion of interactions, risks of dependence and respiratory depression, a plan for short duration, and a safe tapering strategy ^[19].

Common questions in this guide

Are topical NSAIDs safer than oral NSAIDs for osteoarthritis?

Topical NSAIDs such as diclofenac usually result in less medicine reaching the rest of the body than oral NSAID pills, so they may have fewer whole-body risks. They can still irritate the skin and should not be combined with an oral NSAID unless a clinician advises it. They may work less well for deep joints such as the hip.

What are the main risks of oral NSAIDs for osteoarthritis?

Oral NSAIDs can cause stomach ulcers or bleeding, raise blood pressure, increase heart risks, and reduce blood flow to the kidneys. Risk may be greater in people with kidney disease, dehydration, older age, or medicines such as blood thinners, ACE inhibitors, or diuretics. When they are used, clinicians generally choose the lowest effective dose for the shortest time and may add a stomach-protective medicine for people at higher risk of bleeding.

How much relief do steroid injections provide, and how often can I receive them?

Corticosteroid joint injections often provide meaningful relief for a few weeks to a few months, but the duration varies. There is no universally safe maximum number, and frequent repeat injections may contribute to cartilage loss or temporarily raise blood sugar. A clinician should determine the interval based on your response, joint, diabetes risk, and overall health.

How long should I wait after a steroid injection before joint replacement?

Many surgeons require a waiting period of about three to four months after a steroid injection before joint replacement to reduce the risk of infection. The exact interval is surgeon-specific, so tell your surgical team the date and joint involved for every injection.

Do PRP or stem cell injections regrow cartilage in osteoarthritis?

Current research has not shown that PRP or stem cell treatments reliably regrow cartilage or provide consistent benefit for routine osteoarthritis care. Major guidelines do not recommend these treatments routinely, and they are often paid for out of pocket.

Is acetaminophen effective for osteoarthritis pain?

Acetaminophen may help some people, but its average benefit for osteoarthritis pain is often small. Do not exceed the recommended daily amount, drink alcohol while taking it, or use it without medical guidance if you have liver disease. Check cold and flu products to avoid taking acetaminophen from more than one source.

Are opioids recommended for long-term osteoarthritis pain?

Routine long-term opioid use is generally not recommended for osteoarthritis. Tramadol may be considered in selected people when other options do not work or cannot be used, but any opioid plan should address dependence, breathing problems, medication interactions, short duration, and tapering.

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Curated prompts to bring to your next appointment.

1.Given my medical history (heart, stomach, or kidney health), is an oral NSAID safe for me, or should we start with a topical version?
2.If I take an oral NSAID, do I need to take a second medication to protect my stomach from ulcers?
3.How frequently can I safely receive steroid injections based on your clinic's protocols and my diabetes risk?
4.If I am considering a joint replacement in the near future, how long must I wait after my last injection before having surgery?
5.Why do major guidelines recommend against treatments like PRP or stem cells despite their popularity in the media?

Key takeaways

Topical NSAIDs can relieve knee and hand osteoarthritis pain with less whole-body exposure than oral NSAIDs, but they can still cause adverse effects and should not be combined with oral NSAIDs without medical advice.
Oral NSAIDs can cause stomach bleeding, higher blood pressure, heart risks, and kidney problems, especially with certain health conditions or medicines.
Steroid joint injections often provide short-term relief, but repeat injections and timing before joint replacement require clinician guidance.
Acetaminophen’s average benefit for osteoarthritis is often small, and safe use requires attention to dose, alcohol, liver disease, and combination products.
Major guidelines do not recommend PRP or stem-cell treatments for routine osteoarthritis care, and opioids are generally avoided for long-term use.

References (19)

1
2019 American College of Rheumatology/Arthritis Foundation Guideline for the Management of Osteoarthritis of the Hand, Hip, and Knee.
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PMID: 31908149
2
OARSI guidelines for the non-surgical management of knee, hip, and polyarticular osteoarthritis.
Bannuru RR, Osani MC, Vaysbrot EE, et al.
Osteoarthritis and cartilage 2019; (27(11)):1578-1589 doi:10.1016/j.joca.2019.06.011.
PMID: 31278997
3
Efficacy and safety of topical NSAIDs in the management of osteoarthritis: Evidence from real-life setting trials and surveys.
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Seminars in arthritis and rheumatism 2016; (45(4 Suppl)):S18-21.
PMID: 26806189
4
Safety of Oral Non-Selective Non-Steroidal Anti-Inflammatory Drugs in Osteoarthritis: What Does the Literature Say?
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Drugs & aging 2019; (36(Suppl 1)):15-24 doi:10.1007/s40266-019-00660-1.
PMID: 31073921
5
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da Costa BR, Pereira TV, Saadat P, et al.
BMJ (Clinical research ed.) 2021; (375()):n2321 doi:10.1136/bmj.n2321.
PMID: 34642179
6
Non-steroidal anti-inflammatory drug (NSAID) therapy in patients with hypertension, cardiovascular, renal or gastrointestinal comorbidities: joint APAGE/APLAR/APSDE/APSH/APSN/PoA recommendations.
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PMID: 31937550
7
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Ho KY, Cardosa MS, Chaiamnuay S, et al.
Journal of pain research 2020; (13()):1925-1939 doi:10.2147/JPR.S247781.
PMID: 32821151
8
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Bensa A, Albanese J, Boffa A, et al.
Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 2024; (32(2)):311-322 doi:10.1002/ksa.12057.
PMID: 38294103
9
Efficacy of Intra-Articular Corticosteroid Injection for Nonsurgical Management of Trapeziometacarpal Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Krez AN, Wu KA, Klifto KM, et al.
The Journal of hand surgery 2024; (49(6)):511-525 doi:10.1016/j.jhsa.2024.02.001.
PMID: 38530683
10
The Use of Steroid Injections for Hand and Wrist Pathologies.
Bell RJ, Cervenak R, Flint MI, et al.
Cureus 2025; (17(11)):e97104 doi:10.7759/cureus.97104.
PMID: 41416321
11
Association of intra-articular injection and knee arthroscopy prior to primary knee replacement with the timing and outcomes of surgery: Retrospective cohort study using data from the Clinical Practice Research Datalink GOLD database.
Strang M, Broomfield J, Whitehouse M, et al.
PloS one 2024; (19(11)):e0311947 doi:10.1371/journal.pone.0311947.
PMID: 39570872
12
Intra-articular steroid injections in large joint arthritis: A survey of current practice.
Yaghmour KM, Loumpardias GA, Elbahi A, et al.
Musculoskeletal care 2022; (20(2)):349-353 doi:10.1002/msc.1596.
PMID: 34694056
13
Nonoperative Treatments for Knee Osteoarthritis: An Evaluation of Treatment Characteristics and the Intra-Articular Placebo Effect: A Systematic Review.
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JBJS reviews 2018; (6(7)):e5 doi:10.2106/JBJS.RVW.17.00167.
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14
Efficacy of intra-articular platelet-rich plasma compared with placebo in knee osteoarthritis: A systematic review and meta-analysis.
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15
Injectable therapies for knee osteoarthritis.
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Reumatologia 2021; (59(5)):330-339 doi:10.5114/reum.2021.110612.
PMID: 34819708
16
Should Platelet-Rich Plasma or Stem Cell Therapy Be Used to Treat Osteoarthritis?
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Rheumatic diseases clinics of North America 2019; (45(3)):417-438 doi:10.1016/j.rdc.2019.04.010.
PMID: 31277753
17
Clinical and radiographic comparison of a single LP-PRP injection, a single hyaluronic acid injection and daily NSAID administration with a 52-week follow-up: a randomized controlled trial.
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18
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19
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PMID: 31132298

This page is for informational purposes only and does not constitute medical advice. Your clinician can help you weigh medication and injection choices against your medical history and treatment goals.

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