Vitamin D and Calcium Are Required during Denosumab Treatment in Osteoporosis with Rheumatoid Arthritis

Abstract

The aim of this 12-month retrospective study was to evaluate differences in the outcomes of denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients having osteoporosis (OP) with rheumatoid arthritis (RA). Patients were divided into the denosumab monotherapy group (denosumab group, 22 cases) or denosumab plus vitamin D supplementation group (combination group, 21 cases). We measured serum bone alkaline phosphatase (BAP), N-terminal propeptide of type 1 collagen (P1NP), tartrate-resistant acid phosphatase (TRACP)-5b, and urinary N-terminal telopeptide of type-I collagen (NTX) at baseline, 1 week, and 1, 2, 4, 6, 8, and 12 months. We also assessed bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and bilateral total hips (H-BMD) at baseline and 4, 8, and 12 months. Matrix metalloprotanase-3 (MMP-3), Disease Activity Score-28 C-reactive protein (DAS28-CRP), Simplified Disease Activity Index (SDAI), and Health Assessment Questionnaire-Disability Index (HAQ-DI) were assessed before treatment and at 12 months to evaluate RA conditions. The study results showed that BAP, TRACP-5b, and NTX were significantly decreased, but tended to return to pre-treatment levels around 6 and 12 months in both groups. While L-BMD and H-BMD substantially increased in both groups, H-BMD had become significantly higher in the combination group at 12 months (p < 0.01) as compared with the denosumab group. There were no significant differences between the groups regarding MMP-3, DAS28-CRP, SDAI, or HAQ-DI. Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium significantly increased H-BMD in patients having OP with RA.

Keywords: calcium; denosumab; osteoporosis; rheumatoid arthritis; vitamin D.

Figure 1

Percent changes of serum calcium (a); serum phosphorus (b); serum whole parathyroid hormone (PTH) (c); serum 1,25(OH)₂D₃ (d) over the 12-month study period. Closed circles show the denosumab monotherapy group and closed triangles show the combination group. Single asterisk (*) denotes significant differences (p < 0.05) at each time point compared with pretreatment in denosumab monotherapy.

Figure 2

Percent changes of serum bone-specific alkaline phosphatase (BAP) (a); serum N-terminal propeptide of type 1 procollagen (P1NP) (b); serum tartrate-resistant acid phosphatase (TRACP)-5b (c); urinary cross-linked N-terminal telopeptides of type I collagen (NTX) (d) over the 12-month study period. Closed circles show the denosumab monotherapy group and closed triangles show the combination group. Single asterisk (*) denotes significant differences (p < 0.05) and double asterisks (**) denote significant differences (p < 0.01) at each time point compared with pretreatment in the denosumab monotherapy or combination groups. Single hashtag (#) shows significant differences (p < 0.05) and double hashtags (##) show significant differences (p < 0.01) between the denosumab monotherapy and combination groups at each time point.

Figure 2

Percent changes of serum bone-specific alkaline phosphatase (BAP) (a); serum N-terminal propeptide of type 1 procollagen (P1NP) (b); serum tartrate-resistant acid phosphatase (TRACP)-5b (c); urinary cross-linked N-terminal telopeptides of type I collagen (NTX) (d) over the 12-month study period. Closed circles show the denosumab monotherapy group and closed triangles show the combination group. Single asterisk (*) denotes significant differences (p < 0.05) and double asterisks (**) denote significant differences (p < 0.01) at each time point compared with pretreatment in the denosumab monotherapy or combination groups. Single hashtag (#) shows significant differences (p < 0.05) and double hashtags (##) show significant differences (p < 0.01) between the denosumab monotherapy and combination groups at each time point.

Figure 3

Percent changes in lumbar bone mineral density (L-BMD) (a) and bilateral total hip BMD (H-BMD) (b) over the 12-month study period. Closed circles show the denosumab monotherapy group and closed triangles show the combination group. Double asterisks (**) denote significant differences (p < 0.01) at each time point compared with pretreatment in the denosumab monotherapy or combination groups. Double hashtags (##) show significant differences (p < 0.01) between the denosumab monotherapy and combination groups at each time point.