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of infliximab versus placebo in 10 patients with PSC did not show biochemical,
symptomatic, or histologic differences between the two groups after 6 months [ 41 ].
Indeed, it is generally agreed that there is no role for infliximab in the treatment of
PSC, although it may be appropriate for the treatment of UC in patients also affected
by PSC.
Bone Metabolism
Although osteopenia or osteoporosis occurs at higher rates in the IBD population,
the pathophysiology of this association is not fully understood [ 42 ]. The causes are
likely multifactorial; major risk factors include corticosteroid use, calcium and vita-
min D deficiency, age, immobilization, and the inflammatory milieu of the disease
state [ 42 ].
Data regarding the effect of anti-TNF therapy on bone density is not definitive,
but suggests that there may be benefit, possibly by mitigating the inflammatory state
or by a direct effect of TNF antagonism on bone metabolism. Multiple studies have
shown an improvement in biomarkers of bone metabolism in patients with Crohn’s
disease treated with infliximab [ 43 – 45 ]. Others have investigated more clinically
relevant endpoints, particularly bone mineral density (BMD). One study of 46
patients with CD treated with infliximab 5 mg/kg every 6–8 weeks for 1 year had an
increase of BMD of 2–3% at the left femur and lumbar spine. There was no correla-
tion between the change in BMD and baseline osteopenia, steroid use, calcium use,
or changes in CRP [ 46 ]. In a similar trial, 15 CD patients treated with infliximab
were compared retrospectively to 30 CD patients not treated with infliximab.
Patients on infliximab were dosed with 5 mg/kg every 4–8 weeks for a mean period
of 18 months. Lumbar BMD increased in the infliximab group (8.13% ± 7.7%)
despite the control group having more weight gain over the same time span
(22.6 ± 11 months) [ 47 ].
A retrospective trial of 61 patients with CD and low BMD treated with inflix-
imab (23) and/or bisphosphonate (36) also examined changes in BMD. Controlling
for steroid use, patients on both infliximab and a bisphosphonate had a greater
increase in lumbar BMD T-score than those on just a bisphosphonate (6.7%/year vs.
4.5%/year), but infliximab alone had no effect on BMD. Patients on a bisphospho-
nate alone had an increase in lumbar BMD of 4.0% versus a decrease of 3.7% in
those not on a bisphosphonate. The authors speculate that concurrent infliximab
may confer added benefit to therapy with a bisphosphonate alone and that a larger
sample size may have been able to detect a benefit of infliximab alone [ 48 ].
Although the data regarding infliximab and BMD is encouraging, given that it’s
largely retrospective and uncontrolled with small numbers and effect sizes and that
there are available alternative treatments with more substantial supporting evidence,
we would not recommend anti-TNF therapy in IBD patients for the purpose of
improving bone density alone.
D.I. Fudman and S.N. Flier