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Home » Meeting Abstracts » ACR/ARHP Annual Meeting 2012

Abstract Number: 1973

Effect of Adalimumab On the Serum Level of Undercarboxylated Osteocalcin (ucOC), Bone Biochemical Markers and Bone Mineral Density

Yoshitada Sakai1, Akira Hashiramoto2, Takaichi Okano2, Yoshiko Kawasaki3, Nao Shibanuma4 and Masahiro Kurosaka5, 1The Center of Rheumatic Diseases/ Division of Rehabilitation Medicine, Kobe University Hospital, Kobe, Japan, 2The Center for Rheumatic Diseases,, Kobe University Hospital, Kobe, Japan, 3The Center of Rheumatic Diseases, Kobe University Hospital, Kobe, Japan, 4The Center for Rheumatic Diseases, Kobe University Hospital / Departmant of Orthopaedic Surgery, Kobe Kaisei Hospital, Kobe, Japan, 5Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, Kobe, Japan

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Meeting: ACR/ARHP Annual Meeting 2012

Keywords: Adalimumab, bone metabolism, Osteoporosis and vitamins

Session Information

Title: Osteoporosis and Metabolic Bone Disease

Session Type: Abstract Submissions (ACR)

Background/Purpose:

The osteoporotic fracture in patients with rheumatiod arthritis (RA) is caused by systemic osteoporosis as well as periarticular osteoporosis, On the other hand, the serum level of undercarboxylated octeocalcin (ucOC) has been recognized as being a sensitive marker of vitamin K deficiency in bone. A prospective large cohort study showed that increasing the serum level of ucOC predicted hip fracture risk independently of femoral neck bone mineral density (BMD).

Treatments with Adalimumab, a biologic TNF-alfa inhibitor, reduced the hand bone loss of RA patients (PREMIER study), however, the effect of adalimumab on systemic bone metabolism is still unknown.

In this study, we have evaluated the effect of adalimumab on serum ucOC, bone biochemical markers and bone mineral density in patients with RA

Methods:

20 patients with RA were enrolled; 6 females, 4 males, average age 54.5 ±19.2 yrs, average stage 2.4 ± 1.3 and average class 2.1 ± 0.3.  Serum levels of ucOC , cross-linked N-teropeptide of type1 collagen (NTx), bone alkaline phosphatase (BAP) and osteocalcin (OC) were evaluated at 0, 12, 24, 48 weeks after the administration of adalimumab.  BMD were also examined by using dual energy X-ray absorptiometry (DXA) with lumbar spine and femoral neck.  Patients’ disease activities were evaluated by DAS-28 score and mHAQ.  The statistical analysis was performed using one-way repeated measures ANOVA followed by Turkey’s post hoc test.

Results:

The serum levels of ucOC and OC were increased time-dependently and significantly by the administration of adalimumab.(ucOC: p=0.018; 0w vs. 24w, 0w vs. 48w, 12w vs. 48w, OC: p=0.001; 0w vs. 48w, 12w vs. 48w)  The serum levels of NTx was decreased significantly by the administration of adalimumab (p=0.048), whereas the serum levels of BAP (p=0.221) and bone mineral density (L-spine: p=0.334, Femoral neck: p=0.069) did not changed (Table 1).  Variability of disease activity, DAS28 and mHAQ scores did not correlate to bone biochemical markers.

Conclusion:

Treatments with adalimumab increased the serum levels of OC, decreased NTx and thus arrested the systemic bone loss at 48 week.  The increased serum ucOC is caused by the increase of the Vitamin K demand in the bone, presumably due to up-regulation of OC production.  Therefore, during treatments with adalimumab, the vitamin K supplementation is required especially in cases with increased serum ucOC.

Table 1

0w

12w

24w

48w

p-value

ucOC(ng/ml)

3.3±2.1

3.7±2.4

4.4±2.3

5.2±2.7

0.018

OC(ng/ml)

5.3±1.6

6.0±2.3

6.1±2.7

7.5±2.5

0.010

NTx(nmol BCE/l)

16.7±5.3

15.9±3.9

15.4±5.5

14.9±3.2

0.038

BAP(U/I)

13.8±7.2

12.9±5.9

14.7±8.4

15.3±6.8

0.221

DXA L-Spine(g/cm3)

1.007±0.306

n/a

0.852±0.313

0.837±0.328

0.334

DXA F-Neck(g/cm3)

0.732±0.097

n/a

0.726±0.117

0.724±0.109

0.069


Disclosure:

Y. Sakai,
None;

A. Hashiramoto,
None;

T. Okano,
None;

Y. Kawasaki,
None;

N. Shibanuma,
None;

M. Kurosaka,
None.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/effect-of-adalimumab-on-the-serum-level-of-undercarboxylated-osteocalcin-ucoc-bone-biochemical-markers-and-bone-mineral-density/

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