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

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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/