Pretreatment of daily teriparatide enhances the increase of bone mineral density in cortical bones by denosumab therapy.

BACKGROUND: While it is well known that teriparatide (TPTD) increases bone mineral density (BMD) in osteoporotic patients, it is unknown whether TPTD pretreatment affects BMD after denosumab (DMAb) therapy. METHODS: Fifty-seven patients in TPTD-pretreated group and 35 patients in DMAb-alone group had been further analyzed, all of whom were treated by DMAb for 1.5 years. Vitamin D (400 IU) and Ca (600 mg) supplementation was used in all patients. The BMD of lumbar 1-4 vertebrae (L-BMD), bilateral total hips (H-BMD), and bilateral femoral neck (FN-BMD) was quantified at first visit, and at 4, 8, 12, and 18 months after daily TPTD treatment following four times DMAb treatment. RESULTS: There were significant differences in L-BMD (p=0.004) and H-BMD (p=0.026) at baseline between TPTD-pretreated and DMAb-alone groups, although there was no significant difference in FN-BMD between the two groups. The increase of L-BMD by DMAb therapy was less in TPTD-pretreated group than in DMAb-alone group. There was no significant difference in H-BMD, although percent changes of H-BMD tended to be higher in the TPTD-pretreated group than those in the DMAb-alone group. Percent change in FN-BMD at 4 months (p=0.067) and 12 months (p=0.057) tended to be higher in TPTD-pretreated group than in DMAb-alone group. Percent change in FN-BMD at 18 months was significantly higher in TPTD-pretreated group (p=0.004) than in DMAb-alone group. CONCLUSION: These findings suggest that the pretreatment of TPTD might have enhanced the increase of BMD in cortical bones treated by DMAb. Thus, it is favorable that TPTD can be used for osteoporotic patients who have high fracture risks with cortical bones.

Significant improvement of bone mineral density by denosumab treatment in Japanese osteoporotic patients following breast cancer treatment.

BACKGROUND: The aim of this study was to evaluate the effects of denosumab in patients with osteoporosis (OP) and non-metastatic breast cancer following treatment of 1) surgery, 2) surgery and aromatase inhibitors, and 3) surgery, aromatase inhibitors, and anti-cancer agents, compared with those in primary OP patients. PATIENTS AND METHODS: In this retrospective 24-month study, patients were divided into the primary OP group (34 cases) or OP receiving breast cancer treatment group (breast cancer group; 17 cases). We measured serum calcium, whole parathyroid hormone (PTH), 1,25OH2D3, bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase-5b (TRACP-5b), and bone mineral density (BMD) of the lumbar 1-4 vertebrae (L-BMD) and bilateral total hips (H-BMD) for 24 months. RESULTS: The percent changes of serum calcium in the breast cancer group were significantly lower than those in the primary OP group at 1 week, 1 and 12 months. The percent changes of whole PTH in the primary OP group were significantly lower than those in the breast cancer group at 2 and 4 months. Significant differences were found between the groups at 18 months (-34.5% in the primary OP group and -52.6% in the breast cancer group, respectively) for the percent changes of BAP. Significant differences were found between the groups at 12, 18, and 24 months (-39.7% in the primary OP group and -64.0% in the breast cancer group at 24 months, respectively) for the percent changes of TRACP-5b. The percent changes of L-BMD and H-BMD were significantly increased at 12, 18, and 24 months in both the primary OP group (7.0% and 4.7% at 24 months, respectively) and breast cancer group (8.0% and 5.4% at 24 months, respectively), compared with pre-treatment levels. Significant differences were not found between the groups for the percent changes of L-BMD and H-BMD. CONCLUSION: Denosumab significantly increased L-BMD and H-BMD to comparable degrees in both groups; therefore, it represents a good therapeutic option for OP receiving breast cancer treatment as well as primary OP. Also, vitamin D supplementation is required due to the potential hypocalcemia, and estrogen may be responsible for the decrease of serum calcium in the breast cancer patients.

Vitamin D and calcium are required at the time of denosumab administration during osteoporosis treatment.

To evaluate the differences in outcomes of treatment with denosumab alone or denosumab combined with vitamin D and calcium supplementation in patients with primary osteoporosis. Patients were split into a denosumab monotherapy group (18 cases) or a denosumab plus vitamin D supplementation group (combination group; 23 cases). We measured serum bone alkaline phosphatase (BAP), tartrate-resistant acid phosphatase (TRACP)-5b and urinary N-terminal telopeptide of type-I collagen (NTX) at baseline, 1 week, as well as at 1 month and 2, 4, 8 and 12 months. We also measured bone mineral density (BMD) of L1-4 lumbar vertebrae (L)-BMD and bilateral hips (H)-BMD at baseline and at 4, 8 and 12 months. There was no significant difference in patient background. TRACP-5b and urinary NTX were significantly suppressed in both groups from 1 week to 12 months (except at 12 months for NTX). In the combination group, TRACP-5b was significantly decreased compared with the denosumab monotherapy group at 2 and 4 months (P<0.05). BAP was significantly suppressed in both groups at 2-12 months. L-BMD significantly increased at 8 and 12 months (8.9%) in the combination group and at 4, 8 and 12 months (6.0%) in the denosumab monotherapy group, compared with those before treatment. H-BMD was significantly increased in the combination group (3.6%) compared with the denosumab group (1.2%) at 12 months (P<0.05). Compared with denosumab monotherapy, combination therapy of denosumab with vitamin D and calcium stopped the decrease in calcium caused by denosumab, inhibited bone metabolism to a greater extent, and increased BMD (especially at the hips).

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

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 D3 (25(OH)D3) 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)D3, 1,25(OH)2D3, and whole parathyroid hormone (PTH) were also measured. Notably, no fracture occurred during the treatment. Compared with baseline values, 25(OH)D3 levels were significantly increased from 21.6 to 26.4 ng/mL (P = 0.006), despite no vitamin D supplementation. 1,25(OH)2D3 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)D3 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.

Anti-nociceptive effects of elcatonin injection for postmenopausal women with back pain: a randomized controlled trial.

BACKGROUND: Eel calcitonin (elcatonin) injection is widely used for elderly patients suffering from somatic pain in Japan. However, there have been few reports on the analgesic effects of elcatonin injection. The purpose of this study was to examine the analgesic effects of elcatonin injection in postmenopausal women with lower back pain. METHODS: This study was designed as a double-blind, randomized, placebo-controlled study. Thirty-six women aged >/=50 years with acute lower back pain participated in this study. They were randomly divided into two treatment groups according to whether they received a placebo or a weekly trigger point injection of elcatonin (20 units). They were observed for 5 weeks and the extent of pain at motion and at rest according to the visual analog scale (VAS) was evaluated. The mean VAS scores for the elcatonin group were then compared with those of the placebo group. RESULTS: There were no statistically significant differences in the mean VAS scores for pain at rest between the two groups during the 5-week treatment course. However, the mean VAS scores for motion pain in the elcatonin group were significantly lower than those in the placebo group at the third, fifth and sixth weeks. CONCLUSIONS: Elcatonin injection (20 units) significantly relieved motion pain in the lower back in postmenopausal women after three weeks of treatment. This analgesic effect continued for the subsequent 3 weeks.