Increased Serum 25(OH)D₃ Levels in Post-Menopausal Japanese Women with Osteoporosis after 3-Year Bisphosphonate Treatment

Abstract

Osteoporosis is characterized by the systemic impairment of bone mass, strength, and microarchitecture, leading to an increased risk of fragility fracture. Bisphosphonates (BPs) are the first-line drugs for osteoporosis. Vitamin D is considered to be essential for osteoporotic treatment. However, long-term effects of BPs on the serum levels of 25-hydroxyvitamin D 3 (25(OH)D 3 ) are unknown. Accordingly, in this retrospective study, we collected clinical data of 41 post-menopausal Japanese women with osteoporosis treated with BP for over 3 years, without vitamin D supplementation. We measured lumbar and femoral neck bone mineral density (BMD) and serum levels of bone specific alkaline phosphatase (BAP) as a bone formation marker, and tartrate-resistant acid phosphatase (TRACP)-5b as a bone resorption marker, before and after the 3-year treatment. Serum 25(OH)D 3 , 1,25(OH) 2 D 3 , and whole parathyroid hormone (PTH) were also measured. Notably, no fracture occurred during the treatment. Compared with baseline values, 25(OH)D 3 levels were significantly increased from 21.6 to 26.4 ng/mL (P = 0.006), despite no vitamin D supplementation. 1,25(OH) 2 D 3 and whole PTH levels tended to be decreased from 62.6 to 57.8 pg/mL and 27.3 to 25.1 pg/mL, respectively. Both bone formation and resorption markers were significantly suppressed (P < 0.01). Both lumbar BMD (7.3% increase) and femoral neck BMD (4.1% increase) were significantly improved (P < 0.0001) after 3 years of the treatment. Thus, even without vitamin D supplementation, serum 25(OH)D 3 levels were significantly increased after 3-year BP therapy. These results suggest that vitamin D supplementation might not be required in the long-term BP therapy for osteoporosis.

Unexpected rapid increase in bone mineral density by bisphosphonate therapy after multiple spinal fractures: a case report

“…The lack of serum 25(OH)D 3 data is a major limitation of this study. We have previously reported that 4 months of BP therapy significantly decreased 25(OH)D 3 and that 3-year BP therapy without vitamin D supplementation significantly increased 25(OH)D 3 [15, 16]. However, in our patient’s case, BMD rapidly increased; thus, we speculated that 25(OH)D 3 levels might not have had an obvious influence on the results in this study.…”

Additive effects of eldecalcitol in poorly responding long-term bisphosphonate treatment for osteoporosis

“…As adequate levels of serum 25(OH)D 3 are important in osteoporotic treatment, the lack of the data on serum 25(OH)D 3 is another major shortcoming of this study. However, we recently observed that 3-year BP therapy without vitamin D supplementation significantly increased serum 25(OH)D 3 [19]. Although not measured in this study, we presumed that serum 25(OH)D 3 levels were sufficient in our patients owing to their prior long-term BP therapy.…”

Calcium and vitamin D supplementation with 3-year denosumab treatment is beneficial to enhance bone mineral density in postmenopausal patients with osteoporosis and rheumatoid arthritis

“…It was noteworthy that all of the OP patients in those studies had taken vitamin D supplementation 19–22. We previously found that serum 25(OH)D levels were significantly increased after 3-year BP therapy without additional vitamin D in Japanese postmenopausal OP patients 23. On the other hand, serum 25(OH) D had decreased significantly after 4 months of BPs in a Japanese postmenopausal OP cohort 24.…”