Spinal injections, frequently performed in pain medicine practices, are a common intervention for chronic back pain, with an estimated 9 to 11 million injections performed annually in the US alone. Despite their widespread use, studies examining their efficacy have been mixed, with placebo-controlled trials typically finding no effect. [PMID 21914755, PMID 24988555] To further explore the issue, the British Medical Journal convened a panel comprising four patients with chronic spine pain, 10 clinicians experienced in managing chronic spine pain, and eight methodologists. The group reviewed randomized controlled trials and observational studies involving spine procedures and issued the following recommendations:

• The following procedures have no proven benefit and should not be offered for radicular or axial spine pain in the cervical or lumbar region:
• Epidural injection of local anesthetic, steroids, or their combination
• Joint radiofrequency ablation with or without joint targeted injection of local anesthetic plus steroid
• Joint-targeted injection of local anesthetic, steroids, or their combination
• Intramuscular injection of local anesthetic with or without steroids
• Dorsal root ganglion radiofrequency with or without epidural injection of local anesthetic or local anesthetic plus steroids

These recommendations contradict those of the American Society of Interventional Pain Physicians (ASIPP), a professional organization that represents pain management physicians. The 2021 ASIPP guidelines strongly endorse spinal injections for treating chronic lumbar and cervical pain. In their discussion, the ASIPP authors argue that saline or short-acting local anesthetics, frequently used as controls in steroid injection studies, shouldn't be considered placebos because they have an actual therapeutic effect. They go on to contend that single-arm analysis (i.e., looking at therapies individually without comparing them to a control group) is most telling and should receive the majority of emphasis. Huh?

While it's a little comical and slightly disconcerting that a professional association would make an argument to disregard placebo controls in randomized trials, it's not surprising given that they represent doctors who put their kids through college performing these procedures. It also explains how two professional organizations can come to entirely different conclusions analyzing the same evidence. Like most things in life, all you have to do is follow the money.

• BMJ Practice Guideline on Interventional Procedures for Chronic Spine Pain (2025) [PubMed abstract]
• Low back pain review
• Article on a webpage

The FDA recently approved Journavx® (suzetrigine), a novel pain medication with a unique mechanism of action. Suzetrigine is a sodium channel blocker that selectively inhibits NaV1.8 voltage-gated sodium channels, which are expressed in peripheral sensory neurons involved in pain signaling. In a study of 1,118 patients undergoing abdominoplasty, suzetrigine demonstrated similar pain relief to hydrocodone/acetaminophen (5 mg/325 mg every 6 hours) over the first 48 postoperative hours. However, a separate similar study involving 1073 bunionectomy patients found suzetrigine to be superior to placebo but inferior to hydrocodone/APAP.

Suzetrigine's side effect profile is comparable to placebo, and no significant precautions have been identified. The recommended dosage is 100 mg once (on an empty stomach), followed 12 hours later by 50 mg every 12 hours (with or without food). Its use has not been studied beyond 14 days. Suzetrigine is a CYP3A substrate and inducer and should not be administered with strong CYP3A inhibitors. A notable interaction exists with hormonal contraceptives containing progestins other than levonorgestrel and norethindrone. The prescribing information advises that women taking these medications should use additional nonhormonal (e.g., condoms) or alternative contraceptives (e.g., combined oral contraceptives containing levonorgestrel or norethindrone) during treatment and for 28 days after discontinuation.

A novel, non-opioid pain reliever is a significant and much-needed addition. However, like all newly approved drugs, it is expensive and will likely face pushback from insurers. A study comparing it to a high-dose or potent NSAID, such as ketorolac, would be informative.

• Suzetrigine (Journavx®) review
• Opioid medications
• NSAIDs
• Article on webpage

Zoledronate, a bisphosphonate infusion approved to treat osteoporosis, has been shown to prevent fractures in women aged 65 and older with osteopenia (T-score -1 to -2.5). To explore its effects in younger women with bone loss in the osteopenia or less range, researchers randomized 1054 postmenopausal women aged 50 to 60 (average age 56) with a T-score between 0 and -2.5 at the lumbar spine, femoral neck, or total hip (average lumbar spine T-score: -0.43; average total hip T-score: -0.51) to one of three treatments: zoledronate 5 mg at baseline and in 5 years, zoledronate 5 mg at baseline and placebo in 5 years, or placebo at baseline and in 5 years. At 10 years, the primary outcome, morphometric vertebral fracture (fractures identified by their shape on X-ray as opposed to symptoms), occurred in 6.3% (Zoledronate-Zoledronate), 6.6% (Zoledronate-Placebo), and 11.1% (Placebo-Placebo) of patients (p<0.05). Incidences of any fracture were 24.7%, 27.4%., and 35.3%, respectively. (p<0.05). No cases of osteonecrosis of the jaw or atypical femoral fracture, two concerning bisphosphonate side effects, were reported during the trial.

Zoledronate reduced the 10-year fracture risk in postmenopausal women aged 50 to 60 with an average T-score of around -0.46. Two infusions were slightly more effective than one, and both were superior to placebo. A secondary analysis stratifying effect size by baseline bone mineral density (BMD) would have been informative but was not performed. With 45% of women aged 50 to 60 having T-scores less than 0, these results apply to a large population. Current USPSTF guidelines recommend BMD screening in women under 65 at increased risk of osteoporosis, which they loosely define as a 10-year fracture risk of 10% or more.

Providers wanting to incorporate this study into their practice could follow these steps:

1. Screen postmenopausal women aged 50 to 60 with the FRAX tool
2. If the 10-year risk of a major osteoporotic fracture is greater than 10%, order a BMD test
3. If the T-score is 0 to -2.5 at the lumbar spine, femoral neck, or total hip, offer a one-time infusion of zoledronate 5 mg, with an anticipated effect of reducing the absolute risk of any fracture over 10 years by 8%

• Zoledronate vs Placebo in Postmenopausal Women Aged 50 to 60, NEJM (2025)
• Osteoporosis review
• Article on webpage

In 2010, the ACCORD study (N=4733) was published, which found that an intensive blood pressure treatment strategy (target systolic blood pressure [SBP] < 120) did not significantly improve cardiovascular disease (CVD) outcomes compared to a standard strategy (target SBP < 140) in diabetics with hypertension. However, subsequent large trials showed that lower SBP targets (<120-130) improved CVD outcomes across a broad range of patients with and without diabetes. Given the discrepant findings, researchers decided to revisit the issue in diabetics by performing the BPROAD study, where 12,821 hypertensive type two diabetics at increased risk of CVD were randomized to an intensive (target SBP < 120) or standard (target SBP < 140) blood pressure treatment strategy; average SBP one year into the study was 122 mmHg in the intensive group and 135 mmHg in the standard group. After a median follow-up of 4.2 years, a composite of CVD events was significantly lower in the intensive group (1.65%/year vs 2.09%/year, p<0.001). [BPROAD abstract]

Contrary to the 2010 ACCORD trial, BPROAD found that a lower SBP target was beneficial in diabetics with hypertension. Possible reasons for the contradictory findings include (1) lower power in the ACCORD study due to a smaller sample size and (2) the ACCORD study design, which included another factor where patients were randomized to intensive (HgA1C < 6%) or standard (HgA1C 7 - 7.9%) glycemic targets. Other large studies, summarized below, have found that lower SBP targets modestly reduce the absolute risk of CVD events by 1 - 2% in a broad range of patients. While this effect size is small, it is meaningful when applied to large populations. Collectively, these studies support a target SBP of less than 120 mmHg in patients who can tolerate it.

• SPRINT trial (2015): The SPRINT trial (N=9361) compared a target systolic blood pressure (SBP) of <120 mm Hg to a target of <140 mm Hg in nondiabetic individuals at increased risk of CVD. The lower target reduced the incidence of a composite of CVD events by 1.6% over a median follow-up of 3.26 years (5.2% vs 6.8%, p<0.001). [PubMed abstract]
• STEP study (2021): The STEP study (N=8511) compared a target systolic blood pressure (SBP) of <130 mm Hg to a target of <150 mm Hg in Chinese patients 60 to 80 years old with hypertension. The lower target reduced the incidence of a composite of CVD events by 1.1% over a median follow-up of 3.34 years (3.5% vs 4.6%, p=0.007). [PubMed abstract]
• ESPRIT study (2024): The ESPRIT study (N=11,255) compared a target systolic blood pressure (SBP) of <120 mm Hg to a target of <140 mm Hg in Chinese patients at high risk for CVD. The lower target reduced the incidence of a composite of CVD events by 1.4% over a median follow-up of 3.4 years (9.7% vs 11.1%, p=0.028). [PubMed abstract]


• Hypertension treatment guidelines
• Article on webpage

In 2023, colchicine received FDA approval for the secondary prevention of cardiovascular disease (CVD) based on the LoDoCo2 Study (N=5522), which found that it reduced the absolute risk of a composite of CVD events by 2.8% over 29 months. [LoDoCo2 abstract] An earlier 2019 study (COLCOT trial, N=4745) also showed a beneficial effect in patients with recent myocardial infarction (MI). [COLCOT abstract] To expand on these findings, researchers conducted the CLEAR study, where 7062 patients with a recent MI who had undergone percutaneous coronary intervention (PCI) were randomized to colchicine 0.5 mg once daily or placebo. After a median follow-up of 3 years, the primary outcome (a composite of death from cardiovascular causes, recurrent myocardial infarction, stroke, or unplanned ischemia-driven coronary revascularization) was not significantly different between groups (colchicine - 9.1%, Placebo - 9.3%, p=0.93). The study also included a second randomization to spironolactone or placebo. Results from that comparison were also negative.

Despite two prior positive studies, colchicine failed to improve CVD outcomes in the larger CLEAR study. Reasons for the discrepant findings are uncertain but may include CLEAR's high dropout rate (25%) and its two-by-two factorial design that included spironolactone. Notably, colchicine did not improve mortality in any of the trials, and in LoDoCo2, non-cardiovascular deaths were higher in the colchicine group (HR 1.51 95%CI [0.99 - 2.31]). Collectively, these studies do not make a strong case for the routine use of colchicine in CVD.

One observation from all three trials worth noting is that an increased risk of myopathy from combining colchicine with a statin - a common drug interaction warning - was not observed.

• CLEAR Study - Colchicine vs Placebo after MI, NEJM (2024) [PubMed abstract]
• Colchicine (Lodoco) review
• Article on webpage