Sourav Poddar, MD

Evidence summary

Six studies have evaluated SUA levels in patients with acute gout. Despite variations in diagnostic approach (clinical criteria vs synovial crystal analysis) and definitions of normal SUA (based on laboratory methods and sex), all 6 studies found normal levels in 11% to 49% of patients with acute gout (TABLE 1).

TABLE 1
Serum uric acid and acute gout: The evidence

Elevated SUA can be an indicator of gout—or not
A prospective cohort study of 82 patients at a Veterans Administration rheumatology clinic found elevated SUA to be the most sensitive indicator among various clinical criteria for diagnosing acute gout. However, 3 (11%) of the 28 patients who had crystal-proven gout also had a normal SUA.¹

A second prospective cohort study that evaluated 38 patients during 42 episodes of acute gout in various clinical settings reported a normal SUA in 43% of patients diagnosed on clinical grounds or by joint aspiration.²

Some patients become hyperuricemic after diagnosis
The largest retrospective cohort study evaluated 226 Korean inpatients with acute gout diagnosed either by synovial crystals or American College of Rheumatology (ACR) criteria (TABLE 2). It found that 12% (27) had a normal SUA at diagnosis. Interestingly, 81% became hyperuricemic some time after diagnosis.³

TABLE 2
American College of Rheumatology criteria for classifying acute gouty arthritis

What is a normal SUA value?
Another study reviewed SUA levels in a cohort derived from 2 large prospective RCTs of etoricoxib in patients diagnosed with acute gout by crystal analysis. The proportion of patients with a normal SUA varied substantially according to the definition of a normal value: 32% were normal using a value of 0.48 mmol/L; 11% had normal SUA levels when 0.36 mmol/L was used as the cutoff.⁴

A secondary analysis evaluated the effect of allopurinol on SUA. The proportion of patients on allopurinol with a normal SUA level compared with patients not taking allopurinol was 49% vs 29% using the higher normal cutoff value, and 29% vs 11% using the lower normal value (P<.001).⁴

Two studies find many gout patients with a normal SUA
A Japanese retrospective cohort study using ACR criteria found that nearly half of patients diagnosed with acute gout had a normal SUA level.⁵ A 1967 retrospective examination of Framingham Heart Study data found that one-third of patients clinically diagnosed with gout had a normal level. Some of the patients hadn’t been diagnosed at the time their SUA was measured, however.⁶

Recommendations

The ACR’s 1977 criteria for diagnosing gout include hyperuricemia as one potential indicator.⁷ The European League Against Rheumatism advises that normal SUA levels may accompany crystal-proven gout because uric acid either acts as a negative acute-phase reactant or increases in renal excretion during acute episodes. They conclude that SUA has “limited diagnostic value,” especially during acute gout.⁸

Evidence summary

Six studies have evaluated SUA levels in patients with acute gout. Despite variations in diagnostic approach (clinical criteria vs synovial crystal analysis) and definitions of normal SUA (based on laboratory methods and sex), all 6 studies found normal levels in 11% to 49% of patients with acute gout (TABLE 1).

TABLE 1
Serum uric acid and acute gout: The evidence

Elevated SUA can be an indicator of gout—or not
A prospective cohort study of 82 patients at a Veterans Administration rheumatology clinic found elevated SUA to be the most sensitive indicator among various clinical criteria for diagnosing acute gout. However, 3 (11%) of the 28 patients who had crystal-proven gout also had a normal SUA.¹

A second prospective cohort study that evaluated 38 patients during 42 episodes of acute gout in various clinical settings reported a normal SUA in 43% of patients diagnosed on clinical grounds or by joint aspiration.²

Some patients become hyperuricemic after diagnosis
The largest retrospective cohort study evaluated 226 Korean inpatients with acute gout diagnosed either by synovial crystals or American College of Rheumatology (ACR) criteria (TABLE 2). It found that 12% (27) had a normal SUA at diagnosis. Interestingly, 81% became hyperuricemic some time after diagnosis.³

TABLE 2
American College of Rheumatology criteria for classifying acute gouty arthritis

What is a normal SUA value?
Another study reviewed SUA levels in a cohort derived from 2 large prospective RCTs of etoricoxib in patients diagnosed with acute gout by crystal analysis. The proportion of patients with a normal SUA varied substantially according to the definition of a normal value: 32% were normal using a value of 0.48 mmol/L; 11% had normal SUA levels when 0.36 mmol/L was used as the cutoff.⁴

A secondary analysis evaluated the effect of allopurinol on SUA. The proportion of patients on allopurinol with a normal SUA level compared with patients not taking allopurinol was 49% vs 29% using the higher normal cutoff value, and 29% vs 11% using the lower normal value (P<.001).⁴

Two studies find many gout patients with a normal SUA
A Japanese retrospective cohort study using ACR criteria found that nearly half of patients diagnosed with acute gout had a normal SUA level.⁵ A 1967 retrospective examination of Framingham Heart Study data found that one-third of patients clinically diagnosed with gout had a normal level. Some of the patients hadn’t been diagnosed at the time their SUA was measured, however.⁶

Recommendations

The ACR’s 1977 criteria for diagnosing gout include hyperuricemia as one potential indicator.⁷ The European League Against Rheumatism advises that normal SUA levels may accompany crystal-proven gout because uric acid either acts as a negative acute-phase reactant or increases in renal excretion during acute episodes. They conclude that SUA has “limited diagnostic value,” especially during acute gout.⁸

Evidence summary

Six studies have evaluated SUA levels in patients with acute gout. Despite variations in diagnostic approach (clinical criteria vs synovial crystal analysis) and definitions of normal SUA (based on laboratory methods and sex), all 6 studies found normal levels in 11% to 49% of patients with acute gout (TABLE 1).

TABLE 1
Serum uric acid and acute gout: The evidence

Elevated SUA can be an indicator of gout—or not
A prospective cohort study of 82 patients at a Veterans Administration rheumatology clinic found elevated SUA to be the most sensitive indicator among various clinical criteria for diagnosing acute gout. However, 3 (11%) of the 28 patients who had crystal-proven gout also had a normal SUA.¹

A second prospective cohort study that evaluated 38 patients during 42 episodes of acute gout in various clinical settings reported a normal SUA in 43% of patients diagnosed on clinical grounds or by joint aspiration.²

Some patients become hyperuricemic after diagnosis
The largest retrospective cohort study evaluated 226 Korean inpatients with acute gout diagnosed either by synovial crystals or American College of Rheumatology (ACR) criteria (TABLE 2). It found that 12% (27) had a normal SUA at diagnosis. Interestingly, 81% became hyperuricemic some time after diagnosis.³

TABLE 2
American College of Rheumatology criteria for classifying acute gouty arthritis

What is a normal SUA value?
Another study reviewed SUA levels in a cohort derived from 2 large prospective RCTs of etoricoxib in patients diagnosed with acute gout by crystal analysis. The proportion of patients with a normal SUA varied substantially according to the definition of a normal value: 32% were normal using a value of 0.48 mmol/L; 11% had normal SUA levels when 0.36 mmol/L was used as the cutoff.⁴

A secondary analysis evaluated the effect of allopurinol on SUA. The proportion of patients on allopurinol with a normal SUA level compared with patients not taking allopurinol was 49% vs 29% using the higher normal cutoff value, and 29% vs 11% using the lower normal value (P<.001).⁴

Two studies find many gout patients with a normal SUA
A Japanese retrospective cohort study using ACR criteria found that nearly half of patients diagnosed with acute gout had a normal SUA level.⁵ A 1967 retrospective examination of Framingham Heart Study data found that one-third of patients clinically diagnosed with gout had a normal level. Some of the patients hadn’t been diagnosed at the time their SUA was measured, however.⁶

Recommendations

The ACR’s 1977 criteria for diagnosing gout include hyperuricemia as one potential indicator.⁷ The European League Against Rheumatism advises that normal SUA levels may accompany crystal-proven gout because uric acid either acts as a negative acute-phase reactant or increases in renal excretion during acute episodes. They conclude that SUA has “limited diagnostic value,” especially during acute gout.⁸

Evidence summary

Options for treating Morton’s neuroma include changing shoe type, using insoles or metatarsal pads, taking nonsteroidal anti-inflammatory drugs (NSAIDs), giving corticosteroid or sclerosing alcohol injections, and surgically excising or transposing the offending nerve.^1-3

Different conservative measures produce similar results
A small randomized prospective study of 23 patients compared reduction in neuroma pain using supinatory or pronatory insoles.⁴ No explicit inclusion or exclusion criteria other than clinical diagnosis were mentioned. Neither participants nor evaluators were blind to intervention allocations.

Two patients (13%) dropped out at 1 month. At 12 months, pain reduction in the supination and pronation insole groups was 50% and 45%, respectively (not significant).

Injections improve symptoms with minimal adverse effects

A prospective randomized study of 82 patients compared steroid injections alone with shoe modifications.⁵ Primary outcomes were patient satisfaction (presence or absence of pain), amount of pain, and return of pain.

Steroid injections yielded better patient satisfaction compared with shoe modifications alone at 1 and 6 months. Twenty-three percent of shoe-modification patients achieved complete satisfaction at 1 month, compared with 50% of injection patients (P<.01; number needed to treat [NNT]=3.7). At 6 months, the results were 28.6% satisfaction with shoe modification and 73.5% satisfaction with injection (P<.001; NNT=2.3).

The difference disappeared at 1 year (63% satisfaction with shoe modification compared with 82% satisfaction with injection; P>.05), although patients were allowed to cross over at 6 months. No complications occurred. The study was limited by a high rate of crossover from the shoe modification to the injection group at 6 months, elimination of dropouts from the final analysis, and lack of intent-to-treat analysis.

Another technique uses the sclerosing effects of alcohol⁶ delivered by multiple ultrasound-guided injections over time.^7,8 Improvement of symptoms with no long-term adverse events were reported in several case series, although in each study a small number of patients reported localized pain at the site of injection.^6-10 The TABLE summarizes injection studies.^5-11

TABLE
How injection therapies for Morton’s neuroma compare

Surgery: Consider cost and risk of complications
Most surgical studies enrolled patients who had initially failed conservative treatments. Costs and risks of complications must be weighed, including infection, scar sensitivity, residual pain, sensory deficits, and other wound-related morbidities.

Technique varies considerably among surgeons.¹² A Cochrane systematic review of 3 randomized controlled trials comprising 121 patients concluded that, at most, very limited evidence exists that transposition of the transected plantar digital nerve may yield better long-term results than standard resection.³

In a retrospective case series, 82 patients with primary Morton’s neuroma were treated by a single surgeon and a single technique (dorsal incision and nerve transection).¹³ All patients had failed conservative management with orthotics, shoe modification, and NSAIDs (lidocaine injections were used only to pinpoint neuroma location). Sixty-six (81%) returned for follow-up.

Average follow-up evaluation was 5.8 years. Of the patients who were followed, 85% rated overall satisfaction as excellent or good.

Stepped care gets results
A prospective case series enrolled 115 subjects out of 340 consecutive patients who presented to a private orthopedic clinic with a diagnosis of Morton’s neuroma.¹ The authors assessed a 3-stage protocol of stepped care, progressing to the next stage if improvement was inadequate after 3 months: Stage I comprised patient education, footwear modifications, and a metatarsal pad placed proximal to the involved nerve; stage II, injection of steroids with local anesthetic or local anesthetic alone; and stage III, surgery.

Of 57 patients treated only with footwear modifications, 47 (41%) improved and required no further treatment. Twenty-seven (47%) of the 58 patients who received injections improved and required no further treatment. Of the 24 patients who advanced to stage III, 96% improved with surgery.

Recommendations

No consensus exists regarding definitive treatment of Morton’s neuroma. The American College of Occupational and Environmental Medicine recommends excision of the neuroma if nonsurgical treatment fails.¹⁴

A 2003 Cochrane systematic review of 107 studies found insufficient evidence to assess efficacy of surgical and nonsurgical interventions.³ Stepped care has been adopted by many third-party payers who require conservative care before reimbursing for injections, and treatment with injections before reimbursing for surgery.

Evidence summary

Options for treating Morton’s neuroma include changing shoe type, using insoles or metatarsal pads, taking nonsteroidal anti-inflammatory drugs (NSAIDs), giving corticosteroid or sclerosing alcohol injections, and surgically excising or transposing the offending nerve.^1-3

Different conservative measures produce similar results
A small randomized prospective study of 23 patients compared reduction in neuroma pain using supinatory or pronatory insoles.⁴ No explicit inclusion or exclusion criteria other than clinical diagnosis were mentioned. Neither participants nor evaluators were blind to intervention allocations.

Two patients (13%) dropped out at 1 month. At 12 months, pain reduction in the supination and pronation insole groups was 50% and 45%, respectively (not significant).

Injections improve symptoms with minimal adverse effects

A prospective randomized study of 82 patients compared steroid injections alone with shoe modifications.⁵ Primary outcomes were patient satisfaction (presence or absence of pain), amount of pain, and return of pain.

Steroid injections yielded better patient satisfaction compared with shoe modifications alone at 1 and 6 months. Twenty-three percent of shoe-modification patients achieved complete satisfaction at 1 month, compared with 50% of injection patients (P<.01; number needed to treat [NNT]=3.7). At 6 months, the results were 28.6% satisfaction with shoe modification and 73.5% satisfaction with injection (P<.001; NNT=2.3).

The difference disappeared at 1 year (63% satisfaction with shoe modification compared with 82% satisfaction with injection; P>.05), although patients were allowed to cross over at 6 months. No complications occurred. The study was limited by a high rate of crossover from the shoe modification to the injection group at 6 months, elimination of dropouts from the final analysis, and lack of intent-to-treat analysis.

Another technique uses the sclerosing effects of alcohol⁶ delivered by multiple ultrasound-guided injections over time.^7,8 Improvement of symptoms with no long-term adverse events were reported in several case series, although in each study a small number of patients reported localized pain at the site of injection.^6-10 The TABLE summarizes injection studies.^5-11

TABLE
How injection therapies for Morton’s neuroma compare

Surgery: Consider cost and risk of complications
Most surgical studies enrolled patients who had initially failed conservative treatments. Costs and risks of complications must be weighed, including infection, scar sensitivity, residual pain, sensory deficits, and other wound-related morbidities.

Technique varies considerably among surgeons.¹² A Cochrane systematic review of 3 randomized controlled trials comprising 121 patients concluded that, at most, very limited evidence exists that transposition of the transected plantar digital nerve may yield better long-term results than standard resection.³

In a retrospective case series, 82 patients with primary Morton’s neuroma were treated by a single surgeon and a single technique (dorsal incision and nerve transection).¹³ All patients had failed conservative management with orthotics, shoe modification, and NSAIDs (lidocaine injections were used only to pinpoint neuroma location). Sixty-six (81%) returned for follow-up.

Average follow-up evaluation was 5.8 years. Of the patients who were followed, 85% rated overall satisfaction as excellent or good.

Stepped care gets results
A prospective case series enrolled 115 subjects out of 340 consecutive patients who presented to a private orthopedic clinic with a diagnosis of Morton’s neuroma.¹ The authors assessed a 3-stage protocol of stepped care, progressing to the next stage if improvement was inadequate after 3 months: Stage I comprised patient education, footwear modifications, and a metatarsal pad placed proximal to the involved nerve; stage II, injection of steroids with local anesthetic or local anesthetic alone; and stage III, surgery.

Of 57 patients treated only with footwear modifications, 47 (41%) improved and required no further treatment. Twenty-seven (47%) of the 58 patients who received injections improved and required no further treatment. Of the 24 patients who advanced to stage III, 96% improved with surgery.

Recommendations

No consensus exists regarding definitive treatment of Morton’s neuroma. The American College of Occupational and Environmental Medicine recommends excision of the neuroma if nonsurgical treatment fails.¹⁴

A 2003 Cochrane systematic review of 107 studies found insufficient evidence to assess efficacy of surgical and nonsurgical interventions.³ Stepped care has been adopted by many third-party payers who require conservative care before reimbursing for injections, and treatment with injections before reimbursing for surgery.

Evidence summary

Options for treating Morton’s neuroma include changing shoe type, using insoles or metatarsal pads, taking nonsteroidal anti-inflammatory drugs (NSAIDs), giving corticosteroid or sclerosing alcohol injections, and surgically excising or transposing the offending nerve.^1-3

Different conservative measures produce similar results
A small randomized prospective study of 23 patients compared reduction in neuroma pain using supinatory or pronatory insoles.⁴ No explicit inclusion or exclusion criteria other than clinical diagnosis were mentioned. Neither participants nor evaluators were blind to intervention allocations.

Two patients (13%) dropped out at 1 month. At 12 months, pain reduction in the supination and pronation insole groups was 50% and 45%, respectively (not significant).

Injections improve symptoms with minimal adverse effects

A prospective randomized study of 82 patients compared steroid injections alone with shoe modifications.⁵ Primary outcomes were patient satisfaction (presence or absence of pain), amount of pain, and return of pain.

Steroid injections yielded better patient satisfaction compared with shoe modifications alone at 1 and 6 months. Twenty-three percent of shoe-modification patients achieved complete satisfaction at 1 month, compared with 50% of injection patients (P<.01; number needed to treat [NNT]=3.7). At 6 months, the results were 28.6% satisfaction with shoe modification and 73.5% satisfaction with injection (P<.001; NNT=2.3).

The difference disappeared at 1 year (63% satisfaction with shoe modification compared with 82% satisfaction with injection; P>.05), although patients were allowed to cross over at 6 months. No complications occurred. The study was limited by a high rate of crossover from the shoe modification to the injection group at 6 months, elimination of dropouts from the final analysis, and lack of intent-to-treat analysis.

Another technique uses the sclerosing effects of alcohol⁶ delivered by multiple ultrasound-guided injections over time.^7,8 Improvement of symptoms with no long-term adverse events were reported in several case series, although in each study a small number of patients reported localized pain at the site of injection.^6-10 The TABLE summarizes injection studies.^5-11

TABLE
How injection therapies for Morton’s neuroma compare

Surgery: Consider cost and risk of complications
Most surgical studies enrolled patients who had initially failed conservative treatments. Costs and risks of complications must be weighed, including infection, scar sensitivity, residual pain, sensory deficits, and other wound-related morbidities.

Technique varies considerably among surgeons.¹² A Cochrane systematic review of 3 randomized controlled trials comprising 121 patients concluded that, at most, very limited evidence exists that transposition of the transected plantar digital nerve may yield better long-term results than standard resection.³

In a retrospective case series, 82 patients with primary Morton’s neuroma were treated by a single surgeon and a single technique (dorsal incision and nerve transection).¹³ All patients had failed conservative management with orthotics, shoe modification, and NSAIDs (lidocaine injections were used only to pinpoint neuroma location). Sixty-six (81%) returned for follow-up.

Average follow-up evaluation was 5.8 years. Of the patients who were followed, 85% rated overall satisfaction as excellent or good.

Stepped care gets results
A prospective case series enrolled 115 subjects out of 340 consecutive patients who presented to a private orthopedic clinic with a diagnosis of Morton’s neuroma.¹ The authors assessed a 3-stage protocol of stepped care, progressing to the next stage if improvement was inadequate after 3 months: Stage I comprised patient education, footwear modifications, and a metatarsal pad placed proximal to the involved nerve; stage II, injection of steroids with local anesthetic or local anesthetic alone; and stage III, surgery.

Of 57 patients treated only with footwear modifications, 47 (41%) improved and required no further treatment. Twenty-seven (47%) of the 58 patients who received injections improved and required no further treatment. Of the 24 patients who advanced to stage III, 96% improved with surgery.

Recommendations

No consensus exists regarding definitive treatment of Morton’s neuroma. The American College of Occupational and Environmental Medicine recommends excision of the neuroma if nonsurgical treatment fails.¹⁴

A 2003 Cochrane systematic review of 107 studies found insufficient evidence to assess efficacy of surgical and nonsurgical interventions.³ Stepped care has been adopted by many third-party payers who require conservative care before reimbursing for injections, and treatment with injections before reimbursing for surgery.

Evidence summary

While patients may refer to this condition as “Achilles tendonitis,” the phrase is actually a misnomer. That’s because in tendonitis, the inflammation is limited to the surrounding structures, but doesn’t involve the tendon itself.

Acute symptoms respond to NSAIDs

A Cochrane review of treatments for acute Achilles tendonopathy included 9 randomized trials with a total of 697 patients. Two RCTs showed evidence that NSAIDs alleviate acute symptoms. In 1 trial of 212 patients who received an oral NSAID or placebo for 14 days, significantly fewer patients in the placebo group achieved a good or excellent symptom relief (relative risk [RR]=0.42; 95% confidence interval [CI], 0.21-0.86). A second RCT of 243 patients compared treatment with a topical NSAID to placebo for 21 days; significantly fewer participants who took placebo returned to their pre-injury level of activity (RR=0.78; 95% CI, 0.63-0.95). Low-dose heparin injection, heel pads, topical laser therapy, and peritendinous steroid injection produced no significant decrease in pain compared with placebo.¹

Continue to exercise?

Eccentric calf-muscle training helps chronic tendonopathy

ECMT is an effective intervention for chronic noninsertional Achilles tendonopathy. An observational study of ECMT in 78 patients (101 tendons total) with chronic noninsertional Achilles tendonopathy found that 89% were back to their preinjury activity level after a 12-week regimen of ECMT, as indicated by significantly lower scores on a 100-point visual analog scale (67 at baseline vs 10.2 at 12 weeks; P<0.001).²

An RCT compared ECMT or repetitive shock wave therapy to a “wait-and-see” control group (25 patients in each group). After 4 months, both the ECMT and shock wave therapy groups reported a significant decrease in pain compared with controls (P< 0.001; mean difference in 10-point pain score, 2.4; 95% CI, 1.3-3.5). Sixty percent of participants in the ECMT group reported complete recovery or significant improvement (P<0.001; number needed to treat [NNT]=3; mean difference in 6-point Likert scale=–1.6; 95% CI, –2.4 to 0.8).³

During an ECMT program, patients may be able to continue activity without exacerbating Achilles tendonopathy. An RCT of 38 patients compared rest with eccentric training and continued activity and eccentric training for 12 weeks to 6 months using a pain-monitored model. Both groups showed similar improvement in pain and function when measured with the Swedish version of the Achilles assessment questionnaire (VISA-A-S 100-point scale: 0=worst function, 100=completely recovered). The baseline mean VISA-A-S scores were 57 for both groups; the mean scores after 12 months were 85 for the exercise group and 91 for the rest group.⁴

Another option: The AirHeel brace

An AirHeel brace may be a viable alternative to ECMT, especially if the patient can’t tolerate eccentric muscle training because of pain. The brace was designed for Achilles tendonopathy and posterior heel pain. It applies intermittent compression to minimize swelling and promote circulation.

An RCT evaluated 100 patients with chronic noninsertional Achilles tendonopathy who were treated with ECMT, an AirHeel Brace, or a combination of the 2 for 12 weeks. At 1-year follow-up, all 3 groups showed a significant reduction in pain measured by a 10-point visual analog scale (ECMT 30%, brace 27%, combination 53%; P<0.0001). All the groups also showed significantly improved function as measured by an American Orthopaedic Foot and Ankle Society Score (10%, 10%, and 30%, respectively; P<0.001). No significant differences in outcomes were found across the treatment groups, and 90% of participants reached their preinjury activity level after 1 year.⁴

Shock wave therapy and topical glyceryl trinitrate

The role of repetitive shock wave therapy and topical glyceryl trinitrate in the treatment of chronic noninsertional Achilles tendonopathy is less clear. In a double-blinded RCT of 49 patients, shock wave therapy did not produce better outcomes than placebo.⁵

However, a prospective cohort study of 68 patients found that patients who received shock wave therapy had significantly lower mean visual analog scale scores for pain compared with controls after 1 month (P<0.001), 3 months (P<0.001), and 12 months (P<0.001) of treatment.⁶ In a double-blinded RCT of 65 patients, more patients treated with topical glyceryl trinitrate therapy were asymptomatic during activities of daily living at 6 months compared with placebo (P<0.001).⁷

Both shock wave therapy and topical glyceryl trinitrate may have a significant role to play in treating chronic noninsertional Achilles tendonopathy, but more studies are needed to support their use.

Surgery appears to work better for athletes

Surgery is an option for patients with chronic noninsertional Achilles tendonopathy who have failed conservative measures and a 3- to 6-month rehabilitation program. In a systematic review of 26 studies of patients managed surgically, the mean success rate (full return to preinjury activity level) was 77%. However, a negative correlation was observed between the reported success rate and the overall methods score, a rating of the quality of studies (r=0.53; P<0.01). Only 5 of the studies reviewed were prospective cohort studies; the remaining 21 were retrospective cohort studies and case studies.⁸

Athletes responded significantly better to surgery than nonathletic patients, returning to full activity in 4.5 months compared with 7.1 months for nonathletes (P<0.03). Fewer athletes had surgical complications (9% compared with 19% of nonathletes).⁹ More studies are needed to clarify the role of surgery in managing Achilles tendonopathy.

Recommendations

The American College of Foot and Ankle Surgeons recommends initial management by reducing pressure around the affected area combined with heel lifts, orthotics, NSAID therapy, and physical therapy. Immobilization may be used on a case-by-case basis. Local steroid injections aren’t recommended. Patients with resistant tendonopathy should be referred to a foot and ankle surgeon.¹⁰

Evidence summary

While patients may refer to this condition as “Achilles tendonitis,” the phrase is actually a misnomer. That’s because in tendonitis, the inflammation is limited to the surrounding structures, but doesn’t involve the tendon itself.

Acute symptoms respond to NSAIDs

A Cochrane review of treatments for acute Achilles tendonopathy included 9 randomized trials with a total of 697 patients. Two RCTs showed evidence that NSAIDs alleviate acute symptoms. In 1 trial of 212 patients who received an oral NSAID or placebo for 14 days, significantly fewer patients in the placebo group achieved a good or excellent symptom relief (relative risk [RR]=0.42; 95% confidence interval [CI], 0.21-0.86). A second RCT of 243 patients compared treatment with a topical NSAID to placebo for 21 days; significantly fewer participants who took placebo returned to their pre-injury level of activity (RR=0.78; 95% CI, 0.63-0.95). Low-dose heparin injection, heel pads, topical laser therapy, and peritendinous steroid injection produced no significant decrease in pain compared with placebo.¹

Continue to exercise?

Eccentric calf-muscle training helps chronic tendonopathy

ECMT is an effective intervention for chronic noninsertional Achilles tendonopathy. An observational study of ECMT in 78 patients (101 tendons total) with chronic noninsertional Achilles tendonopathy found that 89% were back to their preinjury activity level after a 12-week regimen of ECMT, as indicated by significantly lower scores on a 100-point visual analog scale (67 at baseline vs 10.2 at 12 weeks; P<0.001).²

An RCT compared ECMT or repetitive shock wave therapy to a “wait-and-see” control group (25 patients in each group). After 4 months, both the ECMT and shock wave therapy groups reported a significant decrease in pain compared with controls (P< 0.001; mean difference in 10-point pain score, 2.4; 95% CI, 1.3-3.5). Sixty percent of participants in the ECMT group reported complete recovery or significant improvement (P<0.001; number needed to treat [NNT]=3; mean difference in 6-point Likert scale=–1.6; 95% CI, –2.4 to 0.8).³

During an ECMT program, patients may be able to continue activity without exacerbating Achilles tendonopathy. An RCT of 38 patients compared rest with eccentric training and continued activity and eccentric training for 12 weeks to 6 months using a pain-monitored model. Both groups showed similar improvement in pain and function when measured with the Swedish version of the Achilles assessment questionnaire (VISA-A-S 100-point scale: 0=worst function, 100=completely recovered). The baseline mean VISA-A-S scores were 57 for both groups; the mean scores after 12 months were 85 for the exercise group and 91 for the rest group.⁴

Another option: The AirHeel brace

An AirHeel brace may be a viable alternative to ECMT, especially if the patient can’t tolerate eccentric muscle training because of pain. The brace was designed for Achilles tendonopathy and posterior heel pain. It applies intermittent compression to minimize swelling and promote circulation.

An RCT evaluated 100 patients with chronic noninsertional Achilles tendonopathy who were treated with ECMT, an AirHeel Brace, or a combination of the 2 for 12 weeks. At 1-year follow-up, all 3 groups showed a significant reduction in pain measured by a 10-point visual analog scale (ECMT 30%, brace 27%, combination 53%; P<0.0001). All the groups also showed significantly improved function as measured by an American Orthopaedic Foot and Ankle Society Score (10%, 10%, and 30%, respectively; P<0.001). No significant differences in outcomes were found across the treatment groups, and 90% of participants reached their preinjury activity level after 1 year.⁴

Shock wave therapy and topical glyceryl trinitrate

The role of repetitive shock wave therapy and topical glyceryl trinitrate in the treatment of chronic noninsertional Achilles tendonopathy is less clear. In a double-blinded RCT of 49 patients, shock wave therapy did not produce better outcomes than placebo.⁵

However, a prospective cohort study of 68 patients found that patients who received shock wave therapy had significantly lower mean visual analog scale scores for pain compared with controls after 1 month (P<0.001), 3 months (P<0.001), and 12 months (P<0.001) of treatment.⁶ In a double-blinded RCT of 65 patients, more patients treated with topical glyceryl trinitrate therapy were asymptomatic during activities of daily living at 6 months compared with placebo (P<0.001).⁷

Both shock wave therapy and topical glyceryl trinitrate may have a significant role to play in treating chronic noninsertional Achilles tendonopathy, but more studies are needed to support their use.

Surgery appears to work better for athletes

Surgery is an option for patients with chronic noninsertional Achilles tendonopathy who have failed conservative measures and a 3- to 6-month rehabilitation program. In a systematic review of 26 studies of patients managed surgically, the mean success rate (full return to preinjury activity level) was 77%. However, a negative correlation was observed between the reported success rate and the overall methods score, a rating of the quality of studies (r=0.53; P<0.01). Only 5 of the studies reviewed were prospective cohort studies; the remaining 21 were retrospective cohort studies and case studies.⁸

Athletes responded significantly better to surgery than nonathletic patients, returning to full activity in 4.5 months compared with 7.1 months for nonathletes (P<0.03). Fewer athletes had surgical complications (9% compared with 19% of nonathletes).⁹ More studies are needed to clarify the role of surgery in managing Achilles tendonopathy.

Recommendations

The American College of Foot and Ankle Surgeons recommends initial management by reducing pressure around the affected area combined with heel lifts, orthotics, NSAID therapy, and physical therapy. Immobilization may be used on a case-by-case basis. Local steroid injections aren’t recommended. Patients with resistant tendonopathy should be referred to a foot and ankle surgeon.¹⁰

Evidence summary

While patients may refer to this condition as “Achilles tendonitis,” the phrase is actually a misnomer. That’s because in tendonitis, the inflammation is limited to the surrounding structures, but doesn’t involve the tendon itself.

Acute symptoms respond to NSAIDs

A Cochrane review of treatments for acute Achilles tendonopathy included 9 randomized trials with a total of 697 patients. Two RCTs showed evidence that NSAIDs alleviate acute symptoms. In 1 trial of 212 patients who received an oral NSAID or placebo for 14 days, significantly fewer patients in the placebo group achieved a good or excellent symptom relief (relative risk [RR]=0.42; 95% confidence interval [CI], 0.21-0.86). A second RCT of 243 patients compared treatment with a topical NSAID to placebo for 21 days; significantly fewer participants who took placebo returned to their pre-injury level of activity (RR=0.78; 95% CI, 0.63-0.95). Low-dose heparin injection, heel pads, topical laser therapy, and peritendinous steroid injection produced no significant decrease in pain compared with placebo.¹

Continue to exercise?

Eccentric calf-muscle training helps chronic tendonopathy

ECMT is an effective intervention for chronic noninsertional Achilles tendonopathy. An observational study of ECMT in 78 patients (101 tendons total) with chronic noninsertional Achilles tendonopathy found that 89% were back to their preinjury activity level after a 12-week regimen of ECMT, as indicated by significantly lower scores on a 100-point visual analog scale (67 at baseline vs 10.2 at 12 weeks; P<0.001).²

An RCT compared ECMT or repetitive shock wave therapy to a “wait-and-see” control group (25 patients in each group). After 4 months, both the ECMT and shock wave therapy groups reported a significant decrease in pain compared with controls (P< 0.001; mean difference in 10-point pain score, 2.4; 95% CI, 1.3-3.5). Sixty percent of participants in the ECMT group reported complete recovery or significant improvement (P<0.001; number needed to treat [NNT]=3; mean difference in 6-point Likert scale=–1.6; 95% CI, –2.4 to 0.8).³

During an ECMT program, patients may be able to continue activity without exacerbating Achilles tendonopathy. An RCT of 38 patients compared rest with eccentric training and continued activity and eccentric training for 12 weeks to 6 months using a pain-monitored model. Both groups showed similar improvement in pain and function when measured with the Swedish version of the Achilles assessment questionnaire (VISA-A-S 100-point scale: 0=worst function, 100=completely recovered). The baseline mean VISA-A-S scores were 57 for both groups; the mean scores after 12 months were 85 for the exercise group and 91 for the rest group.⁴

Another option: The AirHeel brace

An AirHeel brace may be a viable alternative to ECMT, especially if the patient can’t tolerate eccentric muscle training because of pain. The brace was designed for Achilles tendonopathy and posterior heel pain. It applies intermittent compression to minimize swelling and promote circulation.

An RCT evaluated 100 patients with chronic noninsertional Achilles tendonopathy who were treated with ECMT, an AirHeel Brace, or a combination of the 2 for 12 weeks. At 1-year follow-up, all 3 groups showed a significant reduction in pain measured by a 10-point visual analog scale (ECMT 30%, brace 27%, combination 53%; P<0.0001). All the groups also showed significantly improved function as measured by an American Orthopaedic Foot and Ankle Society Score (10%, 10%, and 30%, respectively; P<0.001). No significant differences in outcomes were found across the treatment groups, and 90% of participants reached their preinjury activity level after 1 year.⁴

Shock wave therapy and topical glyceryl trinitrate

The role of repetitive shock wave therapy and topical glyceryl trinitrate in the treatment of chronic noninsertional Achilles tendonopathy is less clear. In a double-blinded RCT of 49 patients, shock wave therapy did not produce better outcomes than placebo.⁵

However, a prospective cohort study of 68 patients found that patients who received shock wave therapy had significantly lower mean visual analog scale scores for pain compared with controls after 1 month (P<0.001), 3 months (P<0.001), and 12 months (P<0.001) of treatment.⁶ In a double-blinded RCT of 65 patients, more patients treated with topical glyceryl trinitrate therapy were asymptomatic during activities of daily living at 6 months compared with placebo (P<0.001).⁷

Both shock wave therapy and topical glyceryl trinitrate may have a significant role to play in treating chronic noninsertional Achilles tendonopathy, but more studies are needed to support their use.

Surgery appears to work better for athletes

Surgery is an option for patients with chronic noninsertional Achilles tendonopathy who have failed conservative measures and a 3- to 6-month rehabilitation program. In a systematic review of 26 studies of patients managed surgically, the mean success rate (full return to preinjury activity level) was 77%. However, a negative correlation was observed between the reported success rate and the overall methods score, a rating of the quality of studies (r=0.53; P<0.01). Only 5 of the studies reviewed were prospective cohort studies; the remaining 21 were retrospective cohort studies and case studies.⁸

Athletes responded significantly better to surgery than nonathletic patients, returning to full activity in 4.5 months compared with 7.1 months for nonathletes (P<0.03). Fewer athletes had surgical complications (9% compared with 19% of nonathletes).⁹ More studies are needed to clarify the role of surgery in managing Achilles tendonopathy.

Recommendations

The American College of Foot and Ankle Surgeons recommends initial management by reducing pressure around the affected area combined with heel lifts, orthotics, NSAID therapy, and physical therapy. Immobilization may be used on a case-by-case basis. Local steroid injections aren’t recommended. Patients with resistant tendonopathy should be referred to a foot and ankle surgeon.¹⁰

Evidence summary

Diabetes mellitus and osteoarthritis commonly overlap in patients, many of whom have looked to the nutritional supplement combination of glucosamine and chondroitin sulfates for pain relief. The effectiveness of these supplements in improving patient-oriented outcomes for osteoarthritis is still being evaluated. However, regardless of their effectiveness they remain popular supplements, representing up to a third of the specialized supplement market in the US.¹

The mechanism by which glucosamine is hypothesized to affect blood glucose involves the roles of glucosamine and the hexosamine biosynthesis pathway in the regulation of glucose transport. Overexpression of enzymes involved in this pathway have led to high levels of glucose and insulin resistance in animals given huge doses of intravenous glucosamine (100–200 times higher than oral therapeutic doses in humans).² Studies have specifically investigated the effects of intravenous glucosamine infusion in healthy humans, and it did not show any effect on insulin sensitivity or plasma glucose.

A Cochrane systematic review of 20 randomized controlled trials (RCTs) including 2570 patients in order to evaluate the effectiveness and toxicity of glucosamine in osteoarthritis found that glucosamine was as safe as placebo in terms of adverse reactions. However, they did not comment specifically on diabetic patients or hyperglycemia per se.³

An RCT published in 2004 tested whether glucose intolerance occurs when healthy adults consume normal, recommended dosages of glucosamine sulfate. Nineteen healthy adults were randomized to receive either 1500 mg of glucosamine sulfate or placebo orally each day for 12 weeks. Three-hour oral glucose tolerance tests were performed using 75 g of dextrose. These occurred before the study, at 6 weeks, and at 12 weeks. There were no significant differences between fasting levels of serum insulin or blood glucose.⁴ Glucosamine sulfate supplementation did not alter serum insulin or plasma glucose during the tests. Limitations to the study include the small number of subjects, the short duration period, and the fact that the tests were performed before the patient’s daily glucosamine dosing.

A recent study examined insulin and glucose levels with and without the simultaneous ingestion of 1500 mg of glucosamine. Sixteen fasting volunteers with osteoarthritis but without known diabetes or glucose intolerance received 7 g of glucose with or without ingestion of 1500 mg glucosamine sulfate. The authors unexpectedly uncovered undiagnosed diabetes or impaired glucose tolerance in 3 subjects. These 3 subjects showed a statistically significant (P=.04) 31% increase in the area under the curve of glucose levels following the test. There was no effect of glucosamine sulfate ingestion on patients with normal baseline glucose testing or on insulin levels. Their results might be important since they are the first to suggest that glucosamine ingestion may affect glucose levels in individuals who have untreated diabetes or glucose intolerance.⁵

One double-blinded RCT evaluated whether oral glucosamine supplementation altered glycosylated hemoglobin (HbA_1c) concentrations for patients with well-controlled diabetes mellitus. Thirty-eight patients were randomized to receive either treatment with glucosamine/chondroitin at the recommended doses or placebo. After 3 months of treatment HbA_1c levels did not change and were not significantly different between groups (P=.2).⁶

Another study addressed whether glucosamine taken at recommended doses for the treatment of osteoarthritis had any detrimental effect on glucose metabolism. Fourteen patients participated and had a baseline 4-hour meal tolerance test and a frequently sampled intravenous glucose tolerance test, before and after 4 weeks of glucosamine sulfate treatment (500 mg orally 3 times daily). After 4 weeks they found no change in fasting plasma glucose, insulin, glucose tolerance, or difference in insulin sensitivity in the group of subjects.⁷ Again, the study was limited by a small subject number and short duration of study.

Recommendations from others

The PDR for Nonprescription Drugs and Dietary Supplements states that “glucosamine is likely safe for patients with diabetes that is well controlled with diet only or with one or two oral antidiabetic agents (HbA_1c less than 6.5%). For patients with higher HbA_1c concentrations or for those requiring insulin, closely monitor blood glucose concentrations.”⁸

The American Pain Society encourages adults with osteoarthritis to take 1500 mg of glucosamine daily as a dietary supplement but does not specifically recommend it as pharmacologic management for pain.⁹ The American College of Rheumatology Subcommittee on Osteoarthritis has no recommendations regarding the use of glucosamine or chondroitin in the treatment of knee osteoarthritis.¹⁰

Evidence summary

Diabetes mellitus and osteoarthritis commonly overlap in patients, many of whom have looked to the nutritional supplement combination of glucosamine and chondroitin sulfates for pain relief. The effectiveness of these supplements in improving patient-oriented outcomes for osteoarthritis is still being evaluated. However, regardless of their effectiveness they remain popular supplements, representing up to a third of the specialized supplement market in the US.¹

The mechanism by which glucosamine is hypothesized to affect blood glucose involves the roles of glucosamine and the hexosamine biosynthesis pathway in the regulation of glucose transport. Overexpression of enzymes involved in this pathway have led to high levels of glucose and insulin resistance in animals given huge doses of intravenous glucosamine (100–200 times higher than oral therapeutic doses in humans).² Studies have specifically investigated the effects of intravenous glucosamine infusion in healthy humans, and it did not show any effect on insulin sensitivity or plasma glucose.

A Cochrane systematic review of 20 randomized controlled trials (RCTs) including 2570 patients in order to evaluate the effectiveness and toxicity of glucosamine in osteoarthritis found that glucosamine was as safe as placebo in terms of adverse reactions. However, they did not comment specifically on diabetic patients or hyperglycemia per se.³

An RCT published in 2004 tested whether glucose intolerance occurs when healthy adults consume normal, recommended dosages of glucosamine sulfate. Nineteen healthy adults were randomized to receive either 1500 mg of glucosamine sulfate or placebo orally each day for 12 weeks. Three-hour oral glucose tolerance tests were performed using 75 g of dextrose. These occurred before the study, at 6 weeks, and at 12 weeks. There were no significant differences between fasting levels of serum insulin or blood glucose.⁴ Glucosamine sulfate supplementation did not alter serum insulin or plasma glucose during the tests. Limitations to the study include the small number of subjects, the short duration period, and the fact that the tests were performed before the patient’s daily glucosamine dosing.

A recent study examined insulin and glucose levels with and without the simultaneous ingestion of 1500 mg of glucosamine. Sixteen fasting volunteers with osteoarthritis but without known diabetes or glucose intolerance received 7 g of glucose with or without ingestion of 1500 mg glucosamine sulfate. The authors unexpectedly uncovered undiagnosed diabetes or impaired glucose tolerance in 3 subjects. These 3 subjects showed a statistically significant (P=.04) 31% increase in the area under the curve of glucose levels following the test. There was no effect of glucosamine sulfate ingestion on patients with normal baseline glucose testing or on insulin levels. Their results might be important since they are the first to suggest that glucosamine ingestion may affect glucose levels in individuals who have untreated diabetes or glucose intolerance.⁵

One double-blinded RCT evaluated whether oral glucosamine supplementation altered glycosylated hemoglobin (HbA_1c) concentrations for patients with well-controlled diabetes mellitus. Thirty-eight patients were randomized to receive either treatment with glucosamine/chondroitin at the recommended doses or placebo. After 3 months of treatment HbA_1c levels did not change and were not significantly different between groups (P=.2).⁶

Another study addressed whether glucosamine taken at recommended doses for the treatment of osteoarthritis had any detrimental effect on glucose metabolism. Fourteen patients participated and had a baseline 4-hour meal tolerance test and a frequently sampled intravenous glucose tolerance test, before and after 4 weeks of glucosamine sulfate treatment (500 mg orally 3 times daily). After 4 weeks they found no change in fasting plasma glucose, insulin, glucose tolerance, or difference in insulin sensitivity in the group of subjects.⁷ Again, the study was limited by a small subject number and short duration of study.

Recommendations from others

The PDR for Nonprescription Drugs and Dietary Supplements states that “glucosamine is likely safe for patients with diabetes that is well controlled with diet only or with one or two oral antidiabetic agents (HbA_1c less than 6.5%). For patients with higher HbA_1c concentrations or for those requiring insulin, closely monitor blood glucose concentrations.”⁸

The American Pain Society encourages adults with osteoarthritis to take 1500 mg of glucosamine daily as a dietary supplement but does not specifically recommend it as pharmacologic management for pain.⁹ The American College of Rheumatology Subcommittee on Osteoarthritis has no recommendations regarding the use of glucosamine or chondroitin in the treatment of knee osteoarthritis.¹⁰

Evidence summary

Diabetes mellitus and osteoarthritis commonly overlap in patients, many of whom have looked to the nutritional supplement combination of glucosamine and chondroitin sulfates for pain relief. The effectiveness of these supplements in improving patient-oriented outcomes for osteoarthritis is still being evaluated. However, regardless of their effectiveness they remain popular supplements, representing up to a third of the specialized supplement market in the US.¹

The mechanism by which glucosamine is hypothesized to affect blood glucose involves the roles of glucosamine and the hexosamine biosynthesis pathway in the regulation of glucose transport. Overexpression of enzymes involved in this pathway have led to high levels of glucose and insulin resistance in animals given huge doses of intravenous glucosamine (100–200 times higher than oral therapeutic doses in humans).² Studies have specifically investigated the effects of intravenous glucosamine infusion in healthy humans, and it did not show any effect on insulin sensitivity or plasma glucose.

A Cochrane systematic review of 20 randomized controlled trials (RCTs) including 2570 patients in order to evaluate the effectiveness and toxicity of glucosamine in osteoarthritis found that glucosamine was as safe as placebo in terms of adverse reactions. However, they did not comment specifically on diabetic patients or hyperglycemia per se.³

An RCT published in 2004 tested whether glucose intolerance occurs when healthy adults consume normal, recommended dosages of glucosamine sulfate. Nineteen healthy adults were randomized to receive either 1500 mg of glucosamine sulfate or placebo orally each day for 12 weeks. Three-hour oral glucose tolerance tests were performed using 75 g of dextrose. These occurred before the study, at 6 weeks, and at 12 weeks. There were no significant differences between fasting levels of serum insulin or blood glucose.⁴ Glucosamine sulfate supplementation did not alter serum insulin or plasma glucose during the tests. Limitations to the study include the small number of subjects, the short duration period, and the fact that the tests were performed before the patient’s daily glucosamine dosing.

A recent study examined insulin and glucose levels with and without the simultaneous ingestion of 1500 mg of glucosamine. Sixteen fasting volunteers with osteoarthritis but without known diabetes or glucose intolerance received 7 g of glucose with or without ingestion of 1500 mg glucosamine sulfate. The authors unexpectedly uncovered undiagnosed diabetes or impaired glucose tolerance in 3 subjects. These 3 subjects showed a statistically significant (P=.04) 31% increase in the area under the curve of glucose levels following the test. There was no effect of glucosamine sulfate ingestion on patients with normal baseline glucose testing or on insulin levels. Their results might be important since they are the first to suggest that glucosamine ingestion may affect glucose levels in individuals who have untreated diabetes or glucose intolerance.⁵

One double-blinded RCT evaluated whether oral glucosamine supplementation altered glycosylated hemoglobin (HbA_1c) concentrations for patients with well-controlled diabetes mellitus. Thirty-eight patients were randomized to receive either treatment with glucosamine/chondroitin at the recommended doses or placebo. After 3 months of treatment HbA_1c levels did not change and were not significantly different between groups (P=.2).⁶

Another study addressed whether glucosamine taken at recommended doses for the treatment of osteoarthritis had any detrimental effect on glucose metabolism. Fourteen patients participated and had a baseline 4-hour meal tolerance test and a frequently sampled intravenous glucose tolerance test, before and after 4 weeks of glucosamine sulfate treatment (500 mg orally 3 times daily). After 4 weeks they found no change in fasting plasma glucose, insulin, glucose tolerance, or difference in insulin sensitivity in the group of subjects.⁷ Again, the study was limited by a small subject number and short duration of study.

Recommendations from others

The PDR for Nonprescription Drugs and Dietary Supplements states that “glucosamine is likely safe for patients with diabetes that is well controlled with diet only or with one or two oral antidiabetic agents (HbA_1c less than 6.5%). For patients with higher HbA_1c concentrations or for those requiring insulin, closely monitor blood glucose concentrations.”⁸

The American Pain Society encourages adults with osteoarthritis to take 1500 mg of glucosamine daily as a dietary supplement but does not specifically recommend it as pharmacologic management for pain.⁹ The American College of Rheumatology Subcommittee on Osteoarthritis has no recommendations regarding the use of glucosamine or chondroitin in the treatment of knee osteoarthritis.¹⁰