Bisphosphonates in the treatment of Charcot neuroarthropathy: a double-blind randomised controlled trial.
OBJECTIVE
The management of charcot neuroarthropathy, a severe disabling condition in diabetic patients with peripheral neuropathy, is currently inadequate with no specific pharmacological treatment available. We undertook a double-blind randomised controlled trial to study the effect of pamidronate, a bisphosphonate, in the management of acute diabetic Charcot neuroarthropathy.


METHODS
Altogether 39 diabetic patients with active Charcot neuroarthropathy from four centres in England were randomised in a double-blind placebo-controlled trial. Patients received a single infusion of 90 mg of pamidronate or placebo (saline). Foot temperatures, symptoms and markers of bone turnover (bone specific alkaline phosphatase and deoxypyridinoline crosslinks) were measured over the 12 months, in 10 visits. All patients also had standard treatment of the Charcot foot.


RESULTS
Mean age of the study group (59 % Type II (non-insulin-dependent) diabetes mellitus) was 56.3 +/- 10.2 years. The mean temperature difference between active and control groups was 3.6 +/- 1.7 degrees C and 3.3 +/- 1.4 degrees C, respectively. There was a fall in temperature of the affected foot in both groups after 2 weeks with a further reduction in temperature in the active group at 4 weeks (active and placebo vs baseline; p = 0.001; p = 0.01, respectively), but no difference was seen between groups. An improvement in symptoms was seen in the active group compared with the placebo group (p < 0.001). Reduction in bone turnover (means +/- SEM) was greater in the active than in the control group. Urinary deoxypyridinoline in the pamidronate treated group fell to 4.4 +/- 0.4 nmol/mmol creatinine at 4 weeks compared with 7.1 +/- 1.0 in the placebo group (p = 0.01) and bone-specific alkaline phosphatase fell to 14.1 +/- 1.2 u/l compared with 18.6 +/- 1.6 u/l after 4 weeks, respectively (p = 0.03).


CONCLUSIONS
The bisphosphonate, pamidronate, given as a single dose leads to a reduction in bone turnover, symptoms and disease activity in diabetic patients with active Charcot neuroarthropathy.
Jude
E B
EB
Department of Medicine and Diabetic Foot Clinic, Manchester Royal Infirmary, Oxford Road, Manchester, UK. ejude@dc.cmht.nwest.nhs.uk
Selby
P L
PL
Burgess
J
J
Lilleystone
P
P
Mawer
E B
EB
Page
S R
SR
Donohoe
M
M
Foster
A V
AV
Edmonds
M E
ME
Boulton
A J
AJ
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001177:Arthropathy, Neurogenic / Q000188:drug therapy* / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001831:Body Temperature; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology; D003929:Diabetic Neuropathies / Q000188:drug therapy* / Q000503:physiopathology; D004164:Diphosphonates / Q000627:therapeutic use*; D004311:Double-Blind Method; D005500:Follow-Up Studies; D005528:Foot; D006801:Humans; D008875:Middle Aged; D009460:Neurologic Examination; D000077268:Pamidronate; D010465:Perception; D012775:Shoes; D013997:Time Factors; D014732:Vibration
D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D004164:Diphosphonates; D000469:Alkaline Phosphatase; D000077268:Pamidronate