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What is the best way to treat Morton’s neuroma?
NO SINGLE TREATMENT HAS BEEN IDENTIFIED in the literature. That said, a protocol of stepped care that showed good results in an uncontrolled trial seems reasonable: patient education and foot-wear or insole changes, followed by corticosteroid injections and, finally, surgery (strength of recommendation [SOR]: C, case series).
Injecting sclerosing alcohol depends on the provider’s access to and comfort with ultrasound, but the evidence is insufficient to recommend it routinely (SOR: C, case series).
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
| Study | Injection materials | Type of study | Number of cases | Average follow-up, (mo) | Average number of injections | Results |
|---|---|---|---|---|---|---|
| Greenfield 19849 | Steroid | Retrospective case series | 67 | 24 | 3 | 80% complete relief |
| Saygi 20055 | Steroid | Prospective quasirandomized injection vs footwear modification | 82 | 12 | 2-3 | 82% vs 63% complete or partial pain relief in 2 groups, respectively |
| Markovic 200811 | Steroid* | Prospective case series | 39 | 9 | 1 | 38% complete satisfaction and 28% satisfaction with minor reservations |
| Dockery 19996 | Alcohol | Prospective case series | 100 | 13 | 5.5 | 89% resolution or improved symptoms |
| Fanucci 20048 | Alcohol* | Prospective case series | 40 | 10 | 4 | 90% resolution or improved symptoms |
| Hughes 20077 | Alcohol* | Prospective case series | 101 | 21.1 | 4.1 | 94% resolution or improved symptoms |
| Mozena 200710 | Alcohol | Retrospective case series | 42 | 11 | 3-7 | 61% resolution or improved symptoms. Patients with ≥5 injections (74%) were more likely to respond (P=.0072) |
| *Ultrasound guided. | ||||||
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.
1. Bennett GL, Graham CE, Mauldin DM. Morton’s interdigital neuroma: a comprehensive treatment protocol. Foot Ankle Int. 1995;16:760-763.
2. Wu KK. Morton’s neuroma and metatarsalgia. Curr Opin Rheumatol. 2000;12:131-142.
3. Thomson CE, Gibson JN, Martin D. Interventions for the treatment of Morton’s neuroma. Cochrane Database Syst Rev. 2004;(3):CD003118.-
4. Kilmartin TE, Wallace WA. Effect of pronation and supination orthosis on Morton’s neuroma and lower extremity function. Foot Ankle Int. 1994;15:256-262.
5. Saygi B, Yildirim Y, Saygi EK, et al. Morton’s neuroma: comparative results of two conservative methods. Foot Ankle Int. 2005;26:556-559.
6. Dockery GL. The treatment of intermetatarsal neuromas with 4% alcohol sclerosing injections. J Foot Ankle Surg. 1999;38:403-408.
7. Hughes RJ, Ali K, Jones H, et al. Treatment of Morton’s neuroma with alcohol injection under sonographic guidance: follow-up of 101 cases. Am J Roentgenol. 2007;188:1535-1539.
8. Fanucci E, Masala S, Fabiano S, et al. Treatment of intermetatarsal Morton’s neuroma with alcohol injection under US guide: 10-month follow-up. Eur Radiol. 2004;14:514-518.
9. Greenfield J, Rea J, Jr, Ilfeld FW. Morton’s interdigital neuroma: indications for treatment by local injections versus surgery. Clin Orthop Relat Res. 1984;185:142-144.
10. Mozena JD, Clifford JT. Efficacy of chemical neurolysis for the treatment of interdigital nerve compression of the foot: a retrospective study. J Am Podiatr Med Assoc. 2007;97:203-206.
11. Markovic M, Crichton K, Read JW, et al. Effectiveness of ultrasound-guided corticosteroid injection in the treatment of Morton’s neuroma. Foot Ankle Int. 2008;29:483-487.
12. Hassouna H, Singh D. Morton’s metatarsalgia: pathogenesis, aetiology and current management. Acta Orthop Belg. 2005;71:646-655.
13. Coughlin MJ, Pinsonneault T. Operative treatment of interdigital neuroma: a long-term follow-up study. J Bone Joint Surg Am. 2001;83-A:1321-1328.
14. Clinical Practice Guideline Forefoot Disorders Panel, Thomas JL, Blitch EL, IV, Chaney DM, et al. Diagnosis and treatment of forefoot disorders. Section 3. Morton’s intermetatarsal neuroma. J Foot Ankle Surg. 2009;48:251-256.Available at: . Accessed July 5, 2010.
NO SINGLE TREATMENT HAS BEEN IDENTIFIED in the literature. That said, a protocol of stepped care that showed good results in an uncontrolled trial seems reasonable: patient education and foot-wear or insole changes, followed by corticosteroid injections and, finally, surgery (strength of recommendation [SOR]: C, case series).
Injecting sclerosing alcohol depends on the provider’s access to and comfort with ultrasound, but the evidence is insufficient to recommend it routinely (SOR: C, case series).
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
| Study | Injection materials | Type of study | Number of cases | Average follow-up, (mo) | Average number of injections | Results |
|---|---|---|---|---|---|---|
| Greenfield 19849 | Steroid | Retrospective case series | 67 | 24 | 3 | 80% complete relief |
| Saygi 20055 | Steroid | Prospective quasirandomized injection vs footwear modification | 82 | 12 | 2-3 | 82% vs 63% complete or partial pain relief in 2 groups, respectively |
| Markovic 200811 | Steroid* | Prospective case series | 39 | 9 | 1 | 38% complete satisfaction and 28% satisfaction with minor reservations |
| Dockery 19996 | Alcohol | Prospective case series | 100 | 13 | 5.5 | 89% resolution or improved symptoms |
| Fanucci 20048 | Alcohol* | Prospective case series | 40 | 10 | 4 | 90% resolution or improved symptoms |
| Hughes 20077 | Alcohol* | Prospective case series | 101 | 21.1 | 4.1 | 94% resolution or improved symptoms |
| Mozena 200710 | Alcohol | Retrospective case series | 42 | 11 | 3-7 | 61% resolution or improved symptoms. Patients with ≥5 injections (74%) were more likely to respond (P=.0072) |
| *Ultrasound guided. | ||||||
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.
NO SINGLE TREATMENT HAS BEEN IDENTIFIED in the literature. That said, a protocol of stepped care that showed good results in an uncontrolled trial seems reasonable: patient education and foot-wear or insole changes, followed by corticosteroid injections and, finally, surgery (strength of recommendation [SOR]: C, case series).
Injecting sclerosing alcohol depends on the provider’s access to and comfort with ultrasound, but the evidence is insufficient to recommend it routinely (SOR: C, case series).
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
| Study | Injection materials | Type of study | Number of cases | Average follow-up, (mo) | Average number of injections | Results |
|---|---|---|---|---|---|---|
| Greenfield 19849 | Steroid | Retrospective case series | 67 | 24 | 3 | 80% complete relief |
| Saygi 20055 | Steroid | Prospective quasirandomized injection vs footwear modification | 82 | 12 | 2-3 | 82% vs 63% complete or partial pain relief in 2 groups, respectively |
| Markovic 200811 | Steroid* | Prospective case series | 39 | 9 | 1 | 38% complete satisfaction and 28% satisfaction with minor reservations |
| Dockery 19996 | Alcohol | Prospective case series | 100 | 13 | 5.5 | 89% resolution or improved symptoms |
| Fanucci 20048 | Alcohol* | Prospective case series | 40 | 10 | 4 | 90% resolution or improved symptoms |
| Hughes 20077 | Alcohol* | Prospective case series | 101 | 21.1 | 4.1 | 94% resolution or improved symptoms |
| Mozena 200710 | Alcohol | Retrospective case series | 42 | 11 | 3-7 | 61% resolution or improved symptoms. Patients with ≥5 injections (74%) were more likely to respond (P=.0072) |
| *Ultrasound guided. | ||||||
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.
1. Bennett GL, Graham CE, Mauldin DM. Morton’s interdigital neuroma: a comprehensive treatment protocol. Foot Ankle Int. 1995;16:760-763.
2. Wu KK. Morton’s neuroma and metatarsalgia. Curr Opin Rheumatol. 2000;12:131-142.
3. Thomson CE, Gibson JN, Martin D. Interventions for the treatment of Morton’s neuroma. Cochrane Database Syst Rev. 2004;(3):CD003118.-
4. Kilmartin TE, Wallace WA. Effect of pronation and supination orthosis on Morton’s neuroma and lower extremity function. Foot Ankle Int. 1994;15:256-262.
5. Saygi B, Yildirim Y, Saygi EK, et al. Morton’s neuroma: comparative results of two conservative methods. Foot Ankle Int. 2005;26:556-559.
6. Dockery GL. The treatment of intermetatarsal neuromas with 4% alcohol sclerosing injections. J Foot Ankle Surg. 1999;38:403-408.
7. Hughes RJ, Ali K, Jones H, et al. Treatment of Morton’s neuroma with alcohol injection under sonographic guidance: follow-up of 101 cases. Am J Roentgenol. 2007;188:1535-1539.
8. Fanucci E, Masala S, Fabiano S, et al. Treatment of intermetatarsal Morton’s neuroma with alcohol injection under US guide: 10-month follow-up. Eur Radiol. 2004;14:514-518.
9. Greenfield J, Rea J, Jr, Ilfeld FW. Morton’s interdigital neuroma: indications for treatment by local injections versus surgery. Clin Orthop Relat Res. 1984;185:142-144.
10. Mozena JD, Clifford JT. Efficacy of chemical neurolysis for the treatment of interdigital nerve compression of the foot: a retrospective study. J Am Podiatr Med Assoc. 2007;97:203-206.
11. Markovic M, Crichton K, Read JW, et al. Effectiveness of ultrasound-guided corticosteroid injection in the treatment of Morton’s neuroma. Foot Ankle Int. 2008;29:483-487.
12. Hassouna H, Singh D. Morton’s metatarsalgia: pathogenesis, aetiology and current management. Acta Orthop Belg. 2005;71:646-655.
13. Coughlin MJ, Pinsonneault T. Operative treatment of interdigital neuroma: a long-term follow-up study. J Bone Joint Surg Am. 2001;83-A:1321-1328.
14. Clinical Practice Guideline Forefoot Disorders Panel, Thomas JL, Blitch EL, IV, Chaney DM, et al. Diagnosis and treatment of forefoot disorders. Section 3. Morton’s intermetatarsal neuroma. J Foot Ankle Surg. 2009;48:251-256.Available at: . Accessed July 5, 2010.
1. Bennett GL, Graham CE, Mauldin DM. Morton’s interdigital neuroma: a comprehensive treatment protocol. Foot Ankle Int. 1995;16:760-763.
2. Wu KK. Morton’s neuroma and metatarsalgia. Curr Opin Rheumatol. 2000;12:131-142.
3. Thomson CE, Gibson JN, Martin D. Interventions for the treatment of Morton’s neuroma. Cochrane Database Syst Rev. 2004;(3):CD003118.-
4. Kilmartin TE, Wallace WA. Effect of pronation and supination orthosis on Morton’s neuroma and lower extremity function. Foot Ankle Int. 1994;15:256-262.
5. Saygi B, Yildirim Y, Saygi EK, et al. Morton’s neuroma: comparative results of two conservative methods. Foot Ankle Int. 2005;26:556-559.
6. Dockery GL. The treatment of intermetatarsal neuromas with 4% alcohol sclerosing injections. J Foot Ankle Surg. 1999;38:403-408.
7. Hughes RJ, Ali K, Jones H, et al. Treatment of Morton’s neuroma with alcohol injection under sonographic guidance: follow-up of 101 cases. Am J Roentgenol. 2007;188:1535-1539.
8. Fanucci E, Masala S, Fabiano S, et al. Treatment of intermetatarsal Morton’s neuroma with alcohol injection under US guide: 10-month follow-up. Eur Radiol. 2004;14:514-518.
9. Greenfield J, Rea J, Jr, Ilfeld FW. Morton’s interdigital neuroma: indications for treatment by local injections versus surgery. Clin Orthop Relat Res. 1984;185:142-144.
10. Mozena JD, Clifford JT. Efficacy of chemical neurolysis for the treatment of interdigital nerve compression of the foot: a retrospective study. J Am Podiatr Med Assoc. 2007;97:203-206.
11. Markovic M, Crichton K, Read JW, et al. Effectiveness of ultrasound-guided corticosteroid injection in the treatment of Morton’s neuroma. Foot Ankle Int. 2008;29:483-487.
12. Hassouna H, Singh D. Morton’s metatarsalgia: pathogenesis, aetiology and current management. Acta Orthop Belg. 2005;71:646-655.
13. Coughlin MJ, Pinsonneault T. Operative treatment of interdigital neuroma: a long-term follow-up study. J Bone Joint Surg Am. 2001;83-A:1321-1328.
14. Clinical Practice Guideline Forefoot Disorders Panel, Thomas JL, Blitch EL, IV, Chaney DM, et al. Diagnosis and treatment of forefoot disorders. Section 3. Morton’s intermetatarsal neuroma. J Foot Ankle Surg. 2009;48:251-256.Available at: . Accessed July 5, 2010.
Evidence-based answers from the Family Physicians Inquiries Network
Do glucosamine and chondroitin worsen blood sugar control in diabetes?
Despite theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin (1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose diabetes is well-controlled, or for those without diabetes or glucose intolerance (SOR: A, consistent, good-quality patient-oriented evidence). Some preliminary evidence suggests that glucosamine may worsen glucose intolerance for patients with untreated or undiagnosed glucose intolerance or diabetes (SOR: C, extrapolation from disease-oriented evidence).
Long-term effects are unknown; however, no compelling theoretical or incidental data suggest that long-term results should be different (SOR: C, expert opinion). Further studies are required to clarify the effects of glucosamine on patients with poorly controlled diabetes or glucose intolerance.
These products seem to be a safe alternative to NSAIDs
Lisa Brandes, MD
University of Wyoming, Cheyenne
Glucosamine/chondroitin is a popular over-the-counter supplement used by many patients; it appears to be without any serious adverse affects or drug interactions. It does not seem to have much effect on blood sugar for patients with diabetes. It may relieve symptoms for some patients with pain due to osteoarthritis. As such, glucosamine/chondroitin seems to be a safe alternative to nonsteroidal antiinflammatory drugs (NSAIDs) for patients with osteoarthritis.
I would monitor blood sugars more frequently for patients with diabetes given the low numbers in the studies cited above. I would avoid glucosamine/chondroitin during pregnancy and lactation for the younger symptomatic female patient. The cost of this product varies widely, and this can be a factor for patients since they are paying out of pocket.
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 (HbA1c) 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 HbA1c 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 (HbA1c less than 6.5%). For patients with higher HbA1c 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
1. Clough T. Specialty ingredients market overview. Chemical Market Reporter, July 2003. Available at: www.health-strategy.com/contentmgr/showdetails.php/id/172. Accessed on October 31, 2006.
2. Anderson JW, Nicolosi RJ, Borzelleca JF. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy. Food Chem Toxicol 2005;43:187-201.
3. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2005;(2):CD002946.-
4. Tannis AJ, Barban J, Conquer JA. Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals. Osteoarthritis Cartilage 2004;12:506-511.
5. Biggee BA, Blinn CM, Nuite M, Silbert JE, McAlindon TE. Effects of oral glucosamine sulphate on serum glucose and insulin during an oral glucose tolerance test of subjects with osteoarthritis. Ann Rheum Dis 2006 Jul 3; [Epub ahead of print].
6. Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. Arch Int Med 2003;163:1587-1590.
7. Yu JG, Boies SM, Olefsky JM. The effect of oral glucosamine sulfate on insulin sensitivity in human subjects. Diabetes Care 2003;26:1941-1942.
8. PDR for Nonprescription Drugs, Dietary Supplements, and Herbs: The Definitive Guide to OTC Medications Montvale, NJ: Thomson PDR, 2006.
9. Pain in osteoarthritis, rheumatoid arthritis, and juvenile chronic arthritis. National Guideline Clearinghouse. July 9, 2003. Updated June 16, 2005. Available at: www.guideline.gov/summary/summary.aspx?doc_id=3691. Accessed on October 31, 2006.
10. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum 2000;43:1905-1915.
Despite theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin (1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose diabetes is well-controlled, or for those without diabetes or glucose intolerance (SOR: A, consistent, good-quality patient-oriented evidence). Some preliminary evidence suggests that glucosamine may worsen glucose intolerance for patients with untreated or undiagnosed glucose intolerance or diabetes (SOR: C, extrapolation from disease-oriented evidence).
Long-term effects are unknown; however, no compelling theoretical or incidental data suggest that long-term results should be different (SOR: C, expert opinion). Further studies are required to clarify the effects of glucosamine on patients with poorly controlled diabetes or glucose intolerance.
These products seem to be a safe alternative to NSAIDs
Lisa Brandes, MD
University of Wyoming, Cheyenne
Glucosamine/chondroitin is a popular over-the-counter supplement used by many patients; it appears to be without any serious adverse affects or drug interactions. It does not seem to have much effect on blood sugar for patients with diabetes. It may relieve symptoms for some patients with pain due to osteoarthritis. As such, glucosamine/chondroitin seems to be a safe alternative to nonsteroidal antiinflammatory drugs (NSAIDs) for patients with osteoarthritis.
I would monitor blood sugars more frequently for patients with diabetes given the low numbers in the studies cited above. I would avoid glucosamine/chondroitin during pregnancy and lactation for the younger symptomatic female patient. The cost of this product varies widely, and this can be a factor for patients since they are paying out of pocket.
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 (HbA1c) 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 HbA1c 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 (HbA1c less than 6.5%). For patients with higher HbA1c 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
Despite theoretical risks based on animal models given high intravenous doses, glucosamine/chondroitin (1500 mg/1200 mg daily) does not adversely affect short-term glycemic control for patients whose diabetes is well-controlled, or for those without diabetes or glucose intolerance (SOR: A, consistent, good-quality patient-oriented evidence). Some preliminary evidence suggests that glucosamine may worsen glucose intolerance for patients with untreated or undiagnosed glucose intolerance or diabetes (SOR: C, extrapolation from disease-oriented evidence).
Long-term effects are unknown; however, no compelling theoretical or incidental data suggest that long-term results should be different (SOR: C, expert opinion). Further studies are required to clarify the effects of glucosamine on patients with poorly controlled diabetes or glucose intolerance.
These products seem to be a safe alternative to NSAIDs
Lisa Brandes, MD
University of Wyoming, Cheyenne
Glucosamine/chondroitin is a popular over-the-counter supplement used by many patients; it appears to be without any serious adverse affects or drug interactions. It does not seem to have much effect on blood sugar for patients with diabetes. It may relieve symptoms for some patients with pain due to osteoarthritis. As such, glucosamine/chondroitin seems to be a safe alternative to nonsteroidal antiinflammatory drugs (NSAIDs) for patients with osteoarthritis.
I would monitor blood sugars more frequently for patients with diabetes given the low numbers in the studies cited above. I would avoid glucosamine/chondroitin during pregnancy and lactation for the younger symptomatic female patient. The cost of this product varies widely, and this can be a factor for patients since they are paying out of pocket.
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 (HbA1c) 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 HbA1c 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 (HbA1c less than 6.5%). For patients with higher HbA1c 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
1. Clough T. Specialty ingredients market overview. Chemical Market Reporter, July 2003. Available at: www.health-strategy.com/contentmgr/showdetails.php/id/172. Accessed on October 31, 2006.
2. Anderson JW, Nicolosi RJ, Borzelleca JF. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy. Food Chem Toxicol 2005;43:187-201.
3. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2005;(2):CD002946.-
4. Tannis AJ, Barban J, Conquer JA. Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals. Osteoarthritis Cartilage 2004;12:506-511.
5. Biggee BA, Blinn CM, Nuite M, Silbert JE, McAlindon TE. Effects of oral glucosamine sulphate on serum glucose and insulin during an oral glucose tolerance test of subjects with osteoarthritis. Ann Rheum Dis 2006 Jul 3; [Epub ahead of print].
6. Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. Arch Int Med 2003;163:1587-1590.
7. Yu JG, Boies SM, Olefsky JM. The effect of oral glucosamine sulfate on insulin sensitivity in human subjects. Diabetes Care 2003;26:1941-1942.
8. PDR for Nonprescription Drugs, Dietary Supplements, and Herbs: The Definitive Guide to OTC Medications Montvale, NJ: Thomson PDR, 2006.
9. Pain in osteoarthritis, rheumatoid arthritis, and juvenile chronic arthritis. National Guideline Clearinghouse. July 9, 2003. Updated June 16, 2005. Available at: www.guideline.gov/summary/summary.aspx?doc_id=3691. Accessed on October 31, 2006.
10. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum 2000;43:1905-1915.
1. Clough T. Specialty ingredients market overview. Chemical Market Reporter, July 2003. Available at: www.health-strategy.com/contentmgr/showdetails.php/id/172. Accessed on October 31, 2006.
2. Anderson JW, Nicolosi RJ, Borzelleca JF. Glucosamine effects in humans: a review of effects on glucose metabolism, side effects, safety considerations and efficacy. Food Chem Toxicol 2005;43:187-201.
3. Towheed TE, Maxwell L, Anastassiades TP, et al. Glucosamine therapy for treating osteoarthritis. Cochrane Database Syst Rev 2005;(2):CD002946.-
4. Tannis AJ, Barban J, Conquer JA. Effect of glucosamine supplementation on fasting and non-fasting plasma glucose and serum insulin concentrations in healthy individuals. Osteoarthritis Cartilage 2004;12:506-511.
5. Biggee BA, Blinn CM, Nuite M, Silbert JE, McAlindon TE. Effects of oral glucosamine sulphate on serum glucose and insulin during an oral glucose tolerance test of subjects with osteoarthritis. Ann Rheum Dis 2006 Jul 3; [Epub ahead of print].
6. Scroggie DA, Albright A, Harris MD. The effect of glucosamine-chondroitin supplementation on glycosylated hemoglobin levels in patients with type 2 diabetes mellitus. Arch Int Med 2003;163:1587-1590.
7. Yu JG, Boies SM, Olefsky JM. The effect of oral glucosamine sulfate on insulin sensitivity in human subjects. Diabetes Care 2003;26:1941-1942.
8. PDR for Nonprescription Drugs, Dietary Supplements, and Herbs: The Definitive Guide to OTC Medications Montvale, NJ: Thomson PDR, 2006.
9. Pain in osteoarthritis, rheumatoid arthritis, and juvenile chronic arthritis. National Guideline Clearinghouse. July 9, 2003. Updated June 16, 2005. Available at: www.guideline.gov/summary/summary.aspx?doc_id=3691. Accessed on October 31, 2006.
10. American College of Rheumatology Subcommittee on Osteoarthritis Guidelines. Recommendations for the medical management of osteoarthritis of the hip and knee: 2000 update. Arthritis Rheum 2000;43:1905-1915.
Evidence-based answers from the Family Physicians Inquiries Network