Two-year clinical outcome of denosumab treatment alone and in combination with teriparatide in Japanese treatment-naive postmenopausal osteoporotic women

Abstract

This randomized prospective study aimed to evaluate the clinical outcome of denosumab treatment alone and in combination with teriparatide in treatment-naive postmenopausal Japanese female patients with osteoporosis. Thirty patients were randomly assigned to two groups: (1) denosumab group (denosumab alone, n=13); and (2) combination group (denosumab+teriparatide, n=17). Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and bone mineral density (BMD) of L1-4 lumbar vertebrae (L-BMD) and bilateral total hips (H-BMD) were determined at the first visit and at various time points up to 24 months post-treatment to determine percentage changes. Serum TRACP-5b and urinary NTX were equally suppressed in both groups and maintained at low levels, with slight increases at 12, 18 and 24 months. BAP was significantly decreased in both groups from 4 to 24 months, with significant differences between the groups at 4, 8 and 15 months (P<0.05). L-BMD was significantly increased at most time points in both groups, with a significant difference between the combination group and denosumab group at 24 months (17.2% increase versus 9.6% increase; P<0.05). There was no significant difference in H-BMD between the two groups, although the levels tended to be higher in the combination group than in the denosumab group (9.5% increase versus 5.6% increase). These findings suggest that denosumab+teriparatide combination therapy may represent an important treatment for primary osteoporotic patients at high risk of vertebral fracture.

Figure 1

Patient distribution. Of 30 patients, 13 were assigned to the denosumab group and 17 were assigned to the combination treatment (denosumab and teriparatide) group. All patients completed the 2-year visit schedule in this study. F, female; M, male.

Figure 2

Percentage changes in serum albumin-corrected calcium (a), serum phosphorus (b), serum tartrate-resistant acid phosphatase (TRACP)-5b (c), and urinary N-terminal telopeptide of type I collagen (NTX) (d) at pretreatment and at 1 week (w), 1, 2, 4, 8, 12, 15, 18, 21 and 24 months (m). Solid line: denosumab group; dotted line: combination (denosumab and teriparatide) group. Results are expressed as mean±s.e. ^#P<0.05, significant difference between the denosumab and combination groups at each time point. **P<0.01, significant difference at 1 week (w), 1, 2, 4, 8, 12, 15, 18, 21 and 24 months (m), compared with pretreatment in either the denosumab or combination group.

Figure 3

Percentage changes in serum bone alkaline phosphatase (BAP) (a), serum whole parathyroid hormone (PTH) (b), and serum 1,25(OH)₂D₃ (c) at pretreatment and at 1 week (w), 1, 2, 4, 8, 12, 15, 18, 21 and 24 months (m). Solid line: denosumab group; dotted line: combination (denosumab and teriparatide) group. Results are expressed as mean±s.e. ^†P<0.05, significant difference between the denosumab and combination groups at each time point. **P<0.01, significant difference at 1 week (w), 1, 2, 4, 8, 12, 15, 18, 21 and 24 months (m) compared with pretreatment in either the denosumab or combination group.

Figure 4

Percentage changes in bone mineral density (BMD) of L1–4 lumbar vertebrae (L-BMD) (a) and bilateral total hips (H-BMD) (b) at the first visit and at 4, 8, 12, 18 and 24 months. Results are expressed as mean±s.e. ^†P<0.05, significant difference between the denosumab and combination groups at each time point. *P<0.05, **P<0.01, significant difference at 4, 8, 12, 15, 18 and 24 months compared with pretreatment in either the denosumab or combination group.