Table 1.
Anti tumor necrosis factor (anti-TNF) therapy and bone mineral density in rheumatoid arthritis
| Ref | Study | FU time | Treatment groups (n) | BMD Hands | BMD Spine | BMD Hip | Findings |
|---|---|---|---|---|---|---|---|
| [67] | Obs | 1 year | T1:INF (26) | ND | BMD increased (+ 3%, P<0.01) | BMD increased (12%, P<0.001) | Δmarkers of bone turnover did not correlated with ΔBMD, but they changed in the expected direction. |
| [68] | Obs | 1 year | T1:INF (36) | ND | Stable BMD (+1.1%, P>0.05) | Stable BMD (−0.3%, P>0.05) | Disease activity improved but ΔBMD were not associated with disease activity, and use of prednisone or bisphosphonates |
| [69] | Obs | 1 year | T1: INF (102) | BMD loss (−0.8%, P<0.05) Response vs. non-response (−0.6% vs. −1.2%, P>0.05) |
Stable BMD (+0.2% ,P>0.05) Response vs. no-response (+0.7% vs. −0.6%, P>0.05) |
Stable BMD (−0.20% , P>0.05) Response vs. non-response (+0.8% vs. −0.7%, P<0.001) |
Osteocalcin increased at week 14 and then remained stable. β-CTx and RANKL decreased during follow-up; but OPG did not change. PDR use was not associated with ΔBMD |
| [70] | Obs | >2 years | T1:INF (52) | BMD loss (−3.1%, P<0.05) | BMD increased (+2.6%, P<0.05) PDR users vs. no PDR users (+6.2% vs. 0.8%, P=0.002) RA≤1 year vs. RA>10 years (+5.5% vs. −0.2%, P=0.009) |
BMD stable (−0.1%, P>0.05) | ΔBMD in spine was associated with concurrent use of prednisone and RA duration |
| [71•] | Obs | 5285.2 py | T1: anti-TNF T2: MTX T3: other DMARD |
Risk of wrist fractures T1≈T2≈T3 | ND | Risk of hip fractures T1≈T2≈T3 | Risk of non-vertebral fracture was similar between treatment groups. |
| [72] | OL | 6 – 12 months | T1:INF (48) | ND | BMD stable | BMD stable | Markers of bone formation remained stable. Markers of bone resorption decreased the first 6 months of treatment but returned to baseline at 1 year |
| [73] | OL | 1 year | T1:INF/ADA (19) | ND | BMD stable | ND | Inflammatory markers and disease activity improved significantly. |
| [74] | OL | 1 year | T1: ADA(46) | ND | BMD stable +0.3% (P>0.05) | BMD stable +0.3% (P>0.05) | Disease activity significantly improved during follow-up. ΔBMD at hip were associated with concomitant use of PDR. |
| [75] | Cohort | 1 year | T1: INF + MTX (90) T2: MTX (99 historical controls) |
ND | BMD stable in T1 (−0.2% , P>0.05) BMD decrease in T2 (−3.9%, P<0.001) |
BMD stable in T1 (+0.2%, P>0.05) BMD decrease inT2 (−2.5%, P<0.001) |
Markers of bone turnover remained stable in both treatment groups. In the INF treated group, ΔBMD were not associated with treatment response. |
| [76] | RCT | 6 months | T1: INF + MTX + PDR (10) T2:ETA + MTX + PDR (11) T3: MTX + PDR (10) |
BMD stable T1 & T2 (+1.3%, P>0.05) T3 (−4.6%, P>0.05) |
BMD stable T1 & T2 (+0.2%, P>0.05) T3 (− 0.8%, P>0.05) |
BMD stable T1 & T2 (+ 0.1, P>0.05), T3 (− 0.6% , p>0.05) |
In the anti-TNF treated group, markers of bone formation increased while markers of bone resorption decreased. In the MTX+PDR treated group no changes in markers of bone turnover were observed |
| [77] | RCT | 1 year | T1 : INF + MTX (10) T2 : MTX + placebo (10) |
BMD loss (−2.4%, P=0.048) ΔBMD T1≈T2 (−2.1 vs. −2.8%, P=0.82) |
BMD stable (+ 1.3% , P=0.36) ΔBMD T1≈T2 (−0.8% vs. −1.8%, P=0.71) |
BMD femoral neck & hip stable −1.8%, P=0.07 & −1.4%, P=0.07 ΔBMD femoral neck T1 ≪T2 (−0.4% vs. −3.4%, P=0.01) ΔBMD total hip T1≪T2 (−0.2% vs. −2.6%, P=0.03) |
BMD loss was lower INF compared to placebo in femoral neck and hip. Inflammation was associated with bone loss in hands and femoral neck. Radiographic damage was associated with bone loss at spine, femoral neck/hip. |
| [78] | RCT | 26, 52, 104 weeks | T1: ADA+MTX (261) T2: ADA (261) T3: MTX (246) |
BMD loss T3>T2>T1 | ND | ND | Bone loss was associated with age, inflammation and treatment regimen |
| [79••] | RCT | 52, 104 weeks | T1: ADA+MTX (214) T2: MTX (188) |
T2: bone loss higher in those with high/moderate disease activity vs. low/remission T1: bone loss similar in high/moderate disease activity and low/remission. |
ND | ND | In MTX groups bone loss was higher non responders compared to responders, but no differences in the combination group In combination group BMD loss was comparable to MTX group on remission. |
| [80] [81] | RCT | 1–2 years | T1: Sequential monotherapy (81) T2: Step-up combination (84) T3 : Combination + PDR (89) T4 :Combination + INF (88) |
BMD loss at year 1 & 2 T3 & T4≪T1 &T2 (all P=0.05) BMD loss associated with disease severity |
BMD loss T1≈T2≈T3≈T4 |
BMD loss T1≈T2≈T3≈T4 | BMD loss higher in hand than hip & spine BMD loss associated with progression of radiographic destruction Biphosphonates associated with reduce BMD loss in spine and hip. |
| [82••] | RCT | 1 year | T1: Continuous remission T2:Low disease T3: High disease |
BMD gain in T1 but not in T2 and T3 | ND | ND | BMD was not associated with previous or current use of anti-TNF or prednisone. |
Abbreviations: Ref, references; FU, follow-up; BMD, bone mineral density; ND, not done; Δ, changes; ≈, similar; Obs, observational; OL, open label; RCT, randomized clinical trial; INF, infliximab; ADA, adalimumab; MTX, methotrexate; PDR, prednisone; OPG, osteoprogetegerin; β-CTx, beta carboxy-terminal cross-linking telopeptide of type I collagen; RANKL, receptor activator of nuclear factor kappa beta ligand; DMARD: disease modifying anti rheumatic drug; vs., versus.