Efficacy and safety of different anti-osteoporotic drugs for the spinal fusion surgery: A network meta-analysis

Table 1 General characteristic of the included studies

Ref.	Location	Study	Surgical indication	Comparator	Control	Number of patients		Age of patients (yr)		Sex (M/F)		Follow up
						Comparator	Control	Comparator	Control	Comparator	Control
Jespersen et al[32], 2019	Denmark	RCT	Spondylolisthesis	Teriparatide	Placebo	41	46	71	70	11/30	7/39	12 mo
Sheng et al[37], 2018	China	RCT	Spondylolisthesis HIVD, spinal stenosis	Zoledronic acid	Placebo	28	28	60.7	63.1	7/21	10/18	12 mo
Ide et al[31], 2018	Japan	RCT	Spinal stenosis	Teriparatide + denosumab	Teriparatide	8	8	73.2	75.0	3/5	0/8	12 mo
Seki et al[36], 2017	Japan	Prospective	Vertebral fracture	Teriparatide	Alendronate/risedronate	33	25	72.5	71.5	0/33	0/25	24 mo
Ebata et al[30], 2017	Japan	RCT	Lumbar degenerative disease	Teriparatide	Placebo	36	38	72.6	70.4	0/36	0/38	6 mo
Cho et al[29], 2017	Korea	Prospective	Spinal stenosis, spondylolisthesis	Teriparatide	Alendronate	23	24	71.0	68.2	0/23	0/24	24 mo
Yagi et al[39], 2016	Japan	Prospective	Posterior long instrumented fusion	Teriparatide	Placebo	43	33	68.6	66.7	0/43	0/33	24 mo
Chen et al[28], 2016	China	RCT	Spondylolisthesis	zoledronic acid	Placebo	33	36	65	63	6/27	7/29	12 mo
Ohtori et al[35], 2013	Japan	RCT	Spondylolisthesis with spinal stenosis	Teriparatide/Risedronate	Placebo	20/20	20	78/75	73	0/20,0/20	0/22	12 mo
Li et al[33], 2012	China	RCT	Non-specific	Zoledronic acid	Placebo	28	25	63.63	63.83	13/28	16/25	12 mo
Nagahama et al[34], 2011	Japan	RCT	Spondylolisthesis and spinal enosis	Alendronate	Placebo	19	17	70.3	67.4	1/18	1/16	12 mo
Wang et al[40], 2021	China	RCT	Transforaminal lumbar interbody fusion	Teriparatide	Zoledronic acid	29	38	66.34	65.89	4/25	3/35	12 mo

RCT: Randomized controlled trials; HIVD: Herniated intervertebral disc.

Table 2 Detailed information of the administration drug, dose and timing of administration

Ref.	Drug	Dose	Route	Timing of administration
Jespersen et al[32], 2019	Teriparatide	20 μg	Subcutaneous	90 d
Sheng et al[37], 2018	Zoledronic acid	5 mg	Intravenous	Intravenous single dose 3 d after surgery
Ide et al[31], 2018	Teriparatide + denosumab	60 mg	Subcutaneously	Administered at 2 and 8 mo following surgery
	Teriparatide	20 μg	Subcutaneous	Administered froma month before surgery to 12 mo after surgery
Seki et al[36], 2017	Teriparatide	20 μg	Subcutaneous	Once a day starting 3 mo before surgery through 21 mo after surgery
Ebata et al[30], 2017	Teriparatide	56.5 μg	Subcutaneous	Once a week starting, 1 wk after surgery for a total of 6 mo
Cho et al[29], 2017	Teriparatide
Yagi et al[39], 2016	Teriparatide	20 μg	Subcutaneous	Once a day from the day of surgery for a total of 18 mo
Chen et al[28], 2016	zoledronic acid	5 mg	Intravenous	Single dose 3 d after surgery
Ohtori et al[35], 2013	Teriparatide/Risedronate	20 μg	Subcutaneous	Once a day starting 2 mo before surgery through 10 mo after surgery
		2.5 mg	Oral	Once a day starting 2 mo before surgery through 10 mo after surgery
Li et al[33], 2012	Zoledronic acid	5 mg	Intravenous	3 d after the surgery
Nagahama et al[34], 2011	Alendronate	35 mg	Oral	Not specified
Wang et al[40], 2021	Teriparatide	20 μg	Subcutaneously	Once daily and continuously for more than 6 mo starting from 1 d after surgery
	Zoledronic acid	5 mg	Intravenously	15 min to 3 d after surgery

Table 3 Efficacy of different comparisons of drugs for fusion rate by ORs and corresponding 95%CI

Alendronate	0.59 (0.15, 2.4)	0.84 (0.11, 5.72)	1.88 (0.64, 5.75)	5.73 (0.48, 77.52)	1 (0.17, 6.13)
1.69 (0.42, 6.82)	Placebo	1.42 (0.26, 7.05)	3.17 (1.36, 7.77)	9.66 (0.9, 121.89)	1.69 (0.55, 5.37)
1.19 (0.17, 8.76)	0.7 (0.14, 3.89)	Risedronate	2.24 (0.48, 12.08)	6.85 (0.44, 123.81)	1.2 (0.17, 9.35)
0.53 (0.17, 1.57)	0.32 (0.13, 0.74)	0.45 (0.08, 2.1)	Teriparatide	3.03 (0.33, 32.49)	0.53 (0.13, 2.26)
0.17 (0.01, 2.08)	0.1 (0.01, 1.11)	0.15 (0.01, 2.25)	0.33 (0.03, 3.05)	Teriparatide + denosumab	0.18 (0.01, 2.47)
1 (0.16, 5.99)	0.59 (0.19, 1.83)	0.83 (0.11, 5.98)	1.88 (0.44, 7.79)	5.68 (0.4, 91.1)	Zoledronic acid

Table 4 Efficacy of different comparisons of drugs for Oswestry disability index by weighted mean differences and corresponding 95%CI

Alendronate	11.85 (-0.98, 24.15)	0.17 (-17.13, 17.05)	-3.57 (-16.04, 8.89)	-8.56 (-28.58, 11.16)	7.85 (-12.25, 27.17)
-11.85 (-24.15, 0.98)	Placebo	-11.68 (-26.12, 2.94)	-15.43 (-27.71, -2.7)	-20.42 (-40.08, -0.43)	-4.01 (-19.31, 11.09)
-0.17 (-17.05, 17.13)	11.68 (-2.94, 26.12)	Risedronate	-3.76 (-18.1, 10.98)	-8.74 (-29.92, 12.56)	7.67 (-13.54, 28.7)
3.57 (-8.89, 16.04)	15.43 (2.7, 27.71)	3.76 (-10.98, 18.1)	Teriparatide	-4.99 (-20.54, 10.47)	11.44 (-8.49, 30.78)
8.56 (-11.16, 28.58)	20.42 (0.43, 40.08)	8.74 (-12.56, 29.92)	4.99 (-10.47, 20.54)	Teriparatide + denosumab	16.43 (-8.94, 41.21)
-7.85 (-27.17, 12.25)	4.01 (-11.09, 19.31)	-7.67 (-28.7, 13.54)	-11.44 (-30.78, 8.49)	-16.43 (-41.21, 8.94)	Zoledronic acid

Table 5 Efficacy of different comparisons of drugs for adverse events by ORs and corresponding 95%CI

Alendronate	0.18 (0.01, 2.18)	0.36 (0.02, 5.83)	0.89 (0.16, 4.76)
5.64 (0.46, 97.29)	Placebo	2 (0.14, 33.59)	4.91 (0.78, 49)
2.8 (0.17, 56.64)	0.5 (0.03, 7.4)	Risedronate	2.46 (0.27, 30.06)
1.13 (0.21, 6.23)	0.2 (0.02, 1.28)	0.41 (0.03, 3.74)	Teriparatide