Effect of teriparatide on improving fracture union in osteoporotic intertrochanteric fractures: A systematic review and meta-analysis

Table 1 Search strategy and results obtained from PubMed, EMBASE, Scopus, and Cochrane

Database	Search strategy	Publications identified, n
PubMed	[“teriparatid*“(All Fields) OR “teriparatid“(All Fields) OR “teriparatide“(MeSH Terms) OR “teriparatide“(All Fields) OR “forteo”(All Fields) OR “teriparatide”(MeSH Terms)] AND [“fracture*”(All Fields] OR “fractures, bone” (MeSH Terms]) AND [“trochanter*” (All Fields) OR “intertrochanteric”(All Fields) OR “pertrochanteral”(All Fields) OR “pertrochanteric”(All Fields) OR “hip”(MeSH Terms) OR “hip”(All Fields)] AND [“osteoporo*”(All Fields) OR “osteoporosis, postmenopausal”(MeSH Terms) OR “osteoporosis”(MeSH Terms)]	479
EMBASE	((teriparatid* or forteo) and fracture* and (trochanter* or intertrochanteric or pertrochanteric or hip) and osteoporo*).mp.	1368
Scopus	Article title, Abstract, Keyword (teriparatid* OR forteo) AND fracture* AND (trochanter* OR intertrochanteric OR pertrochanteric OR hip) AND osteoporo*	758
Cochrane	((teriparatid* or forteo) and fracture* and (trochanter* or intertrochanteric or pertrochanteric or hip) and osteoporo*):ti,ab,kw	235

Table 2 Publication data and major demographic characteristics of the included studies

Ref.	Country	Type of study	Patients, n		Other patient parameters		Follow-up duration		Teriparatide injection parameters: Dose, route, and duration of administration	Control modality parameters: Dose, route, and duration of administration
			Teriparatide group	Control group	Teriparatide group	Control group	Teriparatide group	Control group
Huang et al[21]	Taiwan	Retrospective	47	83	BMD: -4.2 ± 1.3	BMD: -3.9 ± 1.2	Minimum of 12 months	Minimum of 12 months	20 μg/day subcutaneously usually for 18 months (minimum of 12 months) beginning on the day of surgery	None
Kim et al[22]	South Korea	Retrospective	52	60	BMD: -3.4 (-4.9 to -2.8)	BMD: -3.2 (-5.2 to -2.9)	Minimum follow-up was 10 months (average: 1.6 years; range: 0.8-3.0 years)	Minimum follow-up was 10 months (average: 1.6 years; range: 0.8-3.0 years)	20 μg/day subcutaneously for 2 months	None
Rana et al[23]	India	RCT	15	15	BMD (kg/m2): 0.537 ± 0.073	BMD (kg/m2): 0.561 ± 0.081	6 months	6 months	20 μg/day subcutaneously for 6 months	None
Mishra et al[24]	India	RCT	16	15	BMD of all patients < -2.5	BMD of all patients < -2.5	24 weeks	24 weeks	20 μg/day subcutaneously for 24 weeks	None
Aggarwal et al[26]	India	RCT	20	20	BMD: -3.04 ± 0.43	BMD: -3.17 ± 0.73	6 months (24 weeks)	6 months (24 weeks)	20 μg/day subcutaneously for 24 weeks	None
Tanavalee et al[25]	Thailand	RCT	25	25	BMD (g/cm3): Total hip: 0.631 ± 0.211; femoral neck: 0.518 ± 0.156	BMD (g/cm3): Total hip: 0.598 ± 0.220; femoral neck: 0.517 ± 0.201	24 weeks	24 weeks	20 μg/day subcutaneously for 24 weeks	Normal saline

RCT: Randomized controlled trial; BMD: Bone mineral density.

Table 3 Radiological and functional outcome of the included studies

Ref.	Radiological outcome data		Functional outcome data		Complications		BMD
	Teriparatide group	Control group	Teriparatide group	Control group	Teriparatide group	Control group	Teriparatide group	Control group
Huang et al[21]	Union time (weeks): 12.3 ± 1.3; tip apex distance (mm): 22.0 ± 2.0; sliding of lag screw (mm): 3.0 ± 1.0; femoral shortening (mm): 2.0 ± 1.0; varus collapse (degrees): 2.0 ± 1.0	Union time (weeks): 13.6 ± 1.5; tip apex distance (mm): 21.0 ± 2.0; sliding of lag screw (mm): 6.0 ± 2.0; femoral shortening (mm): 8.0 ± 6.0; varus collapse (degrees): 5.0 ± 2.0	SF-12 Physical Component Survey Score; preinjury: 46 ± 9; 3 months: 28 ± 11; 6 months: 37 ± 11; 9 months: 39 ± 11; 12 months: 44 ± 12. SF-12 Mental Component Survey Score; preinjury: 59 ± 12; 3 months: 51 ± 11; 6 months: 54 ± 9; 9 months: 52 ± 11; 12 months: 54 ± 12	SF-12 Physical Component Survey Score; preinjury: 46 ± 8; 3 months: 19 ± 8; 6 months: 28 ± 10; 9 months: 35 ± 10; 12 months: 41 ± 11. SF-12 Mental Component Survey Score; preinjury: 58 ± 13; 3 months: 51 ± 11; 6 months: 53 ± 10; 9 months: 53 ± 11; 12 months: 53 ± 11	Overall complications: 12 (26%); superficial wound infection: 3 (6%); deep wound infection: 0; pneumonia: 4 (9%); urinary tract infection: 4 (9%); delayed union: 0; nonunion: 0; cutting of the lag screw: 1 (2%); implant failure: 0; mortality (not related to fracture): 2 (4%)	Overall complications: 47 (57%); superficial wound infection: 6 (7%); deep wound infection: 0; pneumonia: 13 (16%); urinary tract infection: 17 (20%); delayed union: 0; nonunion: 0; cutting of the lag screw: 11 (13%); implant failure: 0; mortality (not related to fracture): 16 (19%)	Not assessed in follow-up	Not assessed in follow-up
Kim et al[22]	Union rate by: 4 weeks 7%; 8 weeks 57%; 12 weeks 96%; 16 weeks 100%; 20 weeks 100%; 24 weeks 100%	Union rate by: 4 weeks 6%; 8 weeks 41%; 12 weeks 78%; 16 weeks 88%; 20 weeks 98%; 24 weeks 100%	Harris Hip Score after: 2 months 60.5 (10-80); 4 months 65.4 (20-90); 6 months 70.4 (24-90). VAS Pain Score after: 2 months 35.2 (10-80); 4 months 28.4 (5-70); 6 months 21.2 (5-70). VAS Stiffness Score after: 2 months 40.8 (20-90); 4 months 35.9 (10-80); 6 months 30.2 (10-80)	Harris Hip Score after: 2 months 645.2 (10-80); 4 months 55.4 (20-86); 6 months 60.4 (20-86). VAS Pain Score after: 2 months 52.4 (10-90); 4 months 41.5 (10-80); 6 months 32.8 (10-80). VAS Stiffness Score after: 2 months 50.6 (20-90); 4 months 44.8 (10-90); 6 months 32.8 (10-80)	Overall complications: 6 (11%); superficial wound infection: 1; deep wound infection: 0; pneumonia: 0; urinary tract infection: 0; mortality: 0; delayed union: 0; nonunion: 0; malunion: 3; superior cutting of the lag screw: 1; implant failure: 0; lateral screw migration requiring further intervention: 1; varus collapse with screw sliding: 0; avascular necrosis: 0	Overall complications: 17 (28%); superficial wound infection: 2; deep wound infection: 1; pneumonia: 0; urinary tract infection: 0; mortality: 0; delayed union: 0; nonunion: 0; malunion: 8; superior cutting of the lag screw: 2; implant failure: 0; lateral screw migration requiring further intervention: 2; varus collapse with screw sliding: 2; avascular necrosis: 0	Not assessed in follow-up	Not assessed in follow-up
Rana et al[23]	Union time (weeks): 13.33 ± 1.95; migration of helical blade (mm): 3 months 0.82 ± 0.73; 6 months 1.39 ± 1.21; change in neck-shaft angle (degrees) (varus collapse) by: 3 months 1.79 ± 0.72; 6 months 3.04 ± 1.46; femoral shortening (mm) by: 3 months 3.61 ± 2.91; 6 months 5.29 ± 4.10	Union time (weeks): 15.47 ± 1.41; migration of helical blade (mm): 3 months 0.92 ± 0.84; 6 months 1.74 ± 0.82; change in neck-shaft angle (degrees) (varus collapse) by: 3 months 2.14 ± 1.01; 6 months 4.59 ± 2.03; femoral shortening (mm) by: 3 months 3.86 ± 3.12; 6 months 6.04 ± 4.31	Percentage depreciation from Lower Extremity Functional Scale at: 3 months 32.17 ± 1.20; 6 months 24.83 ± 1.24	Percentage depreciation from Lower Extremity Functional Scale at: 3 months 32.83 ± 1.00; 6 months 26.17 ± 1.1	Overall complications: 1 (7%); bed sore: 1; malunion, non-union, or any implant related complications: 0	Overall complications: 1 (6%); bed sore: 1; malunion, non-union, or any implant related complications: 0	Percentage change in hip BMD at 6 months 1.81 ± 1.39%	Percentage change in hip BMD at 6 months 0.97 ± 1.14 %
Mishra et al[24]	Union rate by: 6 weeks 0; 12 weeks 56.25%; 24 weeks 100%. RUSH Score by: 6 weeks 22.20 ± 2.30; 12 weeks 28.6 ± 1.25; 24 weeks 30.0 ± 0.00. Tip-apex distance (mm) (measure of blade migration) by: 6 weeks 26.27 ± 5.87; 12 weeks 25.74 ± 3.35; 24 weeks 24.26 ± 1.92. Change in neck-shaft angle (degrees) (varus collapse) by: 6 weeks 0.24 ± 0.76; 12 weeks 1.91 ± 1.57; 24 weeks 2.86 ± 1.36. Femoral neck shortening (mm) by: 6 weeks 0.09 ± 0.06; 12 weeks 3.22 ± 1.91; 24 weeks 5.13 ± 2.41	Union rate by: 6 weeks 0; 12 weeks 13.33%; 24 weeks 100%. RUSH Score by: 6 weeks 21.53 ± 2.83; 12 weeks 28.03 ± 1.55; 24 weeks 30.0 ± 0.00. Tip-apex distance (mm) (measure of blade migration) by: 6 weeks 25.8 ± 3.36; 12 weeks 23.96 ± 5.41; 24 weeks 22.57 ± 1.33. Change in neck-shaft angle (degrees) (varus collapse) by: 6 weeks 0.62 ± 1.03; 12 weeks 3.52 ± 1.24; 24 weeks 4.94 ± 1.90. Femoral neck shortening (mm) by: 6 weeks 0.15 ± 0.72; 12 weeks 3.72 ± 2.10; 24 weeks 7.02 ± 3.43	Palmer and Parker Score by: 6 weeks 2.60 ± 1.25; 12 weeks 6.86 ± 1.26; 24 weeks 8.86 ± 0.12	Palmer and Parker Score by: 6 weeks 2.46 ± 1.12; 12 weeks 6.53 ± 1.12; 24 weeks 8.6 ± 0.17	Overall complications: 2 (13%); bed sore: 2; malunion, non-union, or any implant related complications: 0	Overall complications: 1 (6%); bed sore: 1; malunion, non-union, or any implant related complications: 0	T-score at: 6 weeks -3.4 ± 0.12; 12 weeks -3.31 ± 0.46; 24 weeks -3.29 ± 0.53	T-score at: 6 weeks -3.36 ± 0.02; 12 weeks -3.02 ± 0.04; 24 weeks -2.86 ± 0.26
Aggarwal et al[26]	50% of the patients achieved union within 8-12 weeks. RUSH Score at: 6 weeks 22.52 ± 2.31; 12 weeks 28.62 ± 1.64; 24 weeks 29.95 ± 0.22	15% of the patients achieved union within 8-12 weeks. RUSH Score at: 6 weeks 22.10 ± 2.87; 12 weeks 27.65 ± 1.47; 24 weeks 29.88 ± 0.33	NA	NA	NA	NA	T-score at 24 weeks -2.83 ± 0.43	T-score at 24 weeks -3.15 ± 0.73
Tanavalee et al[25]	Union time (weeks): 7.44 ± 3.34. Average RUSH Score at the time of fracture union: 24.4 points (range: 22.0-26.4 points)	Union time (weeks): 10.56 ± 4.98. Average RUSH Score at the time of fracture union: 23.2 points (range: 22.0-25.6 points)	Harris Hip Score at: 2 weeks 45.4 ± 14.7; 4 weeks 56.0 ± 15.5; 6 weeks 65.8 ± 14.0; 12 weeks 69.8 ± 17.6; 24 weeks 74.9 ± 17.8. TUGT (s) at: 4 weeks 66.6 ± 16.2; 6 weeks 44.0 ± 12.9; 12 weeks 36.7 ± 13.6; 24 weeks 28.7 ± 11.7. 5 × SST at: 4 weeks 48.6 ± 14.3; 6 weeks 44.0 ± 12.9; 12 weeks 36.7 ± 13.6; 24 weeks 28.0 ± 12.0	Harris Hip Score at: 2 weeks 51.3 ± 13.6; 4 weeks 61.7 ± 14.1; 6 weeks 63.9 ± 14.3; 12 weeks 68.6 ± 19.4; 24 weeks 75.0 ± 16.7. TUGT (s) at: 4 weeks 73.3 ± 21.8; 6 weeks 42.9 ± 20.2; 12 weeks 36.9 ± 18.7; 24 weeks 36.4 ± 15.7. 5 × SST at: 4 weeks 57.6 ± 20.6; 6 weeks 42.9 ± 20.2; 12 weeks 38.8 ± 18.5; 24 weeks 36.4 ± 15.7	Fixation failure: 0; nonunion: 0; injection-related issues: 1 (bruise around the injection site at 2nd-week visit)	Fixation failure: 0; nonunion: 0; injection-related issues: 1 (skin itching around the injection area)	BMD at 24 weeks (g/cm3): Total hip 0.607 ± 0.168; femoral neck: 0.505 ± 0.140	BMD at 24 weeks (g/cm3): Total hip: 0.560 ± 0.168; femoral neck: 0.475 ± 0.138

RUSH: Radiographic Union Score for Hip; SF-12: 12-item short form survey; VAS: Visual Analog Score; NA: Not available; 5 × SST: Five-time sit-to-stand test; TUGT: Time up-and-go test; BMD: Bone mineral density.

Table 4 Methodological index for nonrandomized studies appraisal scores for nonrandomized studies included in the study

Ref.	Type of study (level of evidence)	Methodological items												Total
		11	22	33	44	55	66	77	88	99	1010	1111	1212
Huang et al[21]	Prospective retrospective (III)	2	2	2	2	2	2	1	2	2	2	2	2	23
Kim et al[22]	Retrospective (III)	2	0	1	2	2	2	1	0	2	2	2	2	18

¹A clearly stated aim.

²Inclusion of consecutive patients.

³Prospective collection of data.

⁴Endpoints appropriate to the aim of the study.

⁵Unbiased assessment of the study endpoint.

⁶Follow-up period appropriate to the aim of the study.

⁷Loss to follow-up that is < 5%.

⁸Prospective calculation of the study size.

⁹An adequate control group.

¹⁰Contemporary groups.

¹¹Baseline equivalence of groups.

¹²Adequate statistical analyses.

The items were scored as: 0: Not reported; 1: Reported but inadequate; or 2: Reported and adequate.