Effect of early postoperative administration of zoledronic acid on the prognosis of osteoporotic femoral intertrochanteric fracture in patients with advanced ages

doi:10.3969/j.issn.1674-8115.2024.07.010

Abstract

Abstract:

Objective ·To investigate the effect of early postoperative administration of zoledronic acid on fracture healing and functional recovery in elderly patients with osteoporotic femoral intertrochanteric fracture treated with proximal femoral nail antirotation (PFNA) surgery, and explore other potential prognostic factors. Methods ·A total of 174 patients with femoral intertrochanteric fractures of 80 years old or above who underwent PFNA treatment in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from January, 2016 to February, 2022, were divided into experimental group (n=26) and control group (n=148) according to whether they received zoledronic acid early after surgery. All patients were followed up twice at 6 weeks and 12 weeks after surgery. The patients in the experimental group were matched with the control group by propensity score matching (PSM) at a ratio of 1:3 (the matching factors included age, gender, fracture type, and body mass index). General characteristics, as well as fracture healing and functional recovery at the two follow-up visits were compared between the two groups after matching. Subsequently, Logistic regression was used to explore the potential prognostic factors on fracture healing at 12 weeks after surgery. Results ·PSM resulted in 25 patients in the experimental group and 65 patients in the control group, and there were no statistically significant differences in baseline characteristics between the two groups. The fracture healing rates at 6 weeks and 12 weeks after surgery in the experimental group (16.0% and 96.0%, respectively) were higher than those in the control group (1.5% and 73.8%), and the differences were statistically significant (P<0.05). Harris hip function score in the experimental group at 12 weeks was significantly higher than that of the control group (P=0.019). The results of Logistic regression analysis showed that good surgical reduction (OR=12.52, 95%CI 2.67?58.74, P=0.001), early postoperative administration of zoledronic acid (OR=10.14, 95%CI 1.01?102.09, P=0.049), and higher serum albumin level (OR=1.15, 95%CI 1.02?1.29, P=0.025) were the favorable factors of early fracture healing, while unstable fracture (OR=0.10, 95%CI 0.03?0.31, P=0.000) was the unfavorable factor. Conclusion ·For elderly patients with osteoporotic intertrochanteric femoral fractures treated with PFNA surgery, early postoperative administration of zoledronic acid can promote fracture healing and lead to better functional recovery; in addition, good surgical reduction and higher serum albumin levels are favorable factors for fracture healing, whereas unstable fracture presents as a hindrance to the healing process.

Key words: femoral intertrochanteric fracture, zoledronic acid, osteoporosis, elderly

CLC Number:

R683.42

WANG Beichen, YANG Yaoqi, BAO Qiyuan, WEN Junxiang, ZHANG Weibin, WAN Rong. Effect of early postoperative administration of zoledronic acid on the prognosis of osteoporotic femoral intertrochanteric fracture in patients with advanced ages[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024, 44(7): 891-898.

Figures/Tables 4

TrendMD

References 39

1	EINHORN T A. The cell and molecular biology of fracture healing[J]. Clin Orthop Relat Res, 1998(355 Suppl): S7-S21.
2	LIN J H. Bisphosphonates: a review of their pharmacokinetic properties[J]. Bone, 1996, 18(2): 75-85.
3	ERIKSEN E F, LYLES K W, COLÓN-EMERIC C S, et al. Antifracture efficacy and reduction of mortality in relation to timing of the first dose of zoledronic acid after hip fracture[J]. J Bone Miner Res, 2009, 24(7): 1308-1313.
4	ORCEL P, FUNCK-BRENTANO T. Medical management following an osteoporotic fracture[J]. Orthop Traumatol Surg Res, 2011, 97(8): 860-869.
5	CHATTOPADHYAY A, JAIN S. Fracture prevention with zoledronate in older women with osteopenia[J]. N Engl J Med, 2019, 380(13): 1287-1288.
6	AMANAT N, MCDONALD M, GODFREY C, et al. Optimal timing of a single dose of zoledronic acid to increase strength in rat fracture repair[J]. J Bone Miner Res, 2007, 22(6): 867-876.
7	LENEHAN T M, BALLIGAND M, NUNAMAKER D M, et al. Effect of EHDP on fracture healing in dogs[J]. J Orthop Res, 1985, 3(4): 499-507.
8	ADOLPHSON P, ABBASZADEGAN H, BODÉN H, et al. Clodronate increases mineralization of callus after Colles′ fracture: a randomized, double-blind, placebo-controlled, prospective trial in 32 patients[J]. Acta Orthop Scand, 2000, 71(2): 195-200.
9	KIM T Y, HA Y C, KANG B J, et al. Does early administration of bisphosphonate affect fracture healing in patients with intertrochanteric fractures?[J]. J Bone Joint Surg Br, 2012, 94(7): 956-960.
10	VAN DER POEST CLEMENT E, PATKA P, VANDORMAEL K, et al. The effect of alendronate on bone mass after distal forearm fracture[J]. J Bone Miner Res, 2000, 15(3): 586-593.
11	LI Y, ZHAO W B, WANG D L, et al. Treatment of osteoporotic intertrochanteric fractures by zoledronic acid injection combined with proximal femoral nail anti-rotation[J]. Chin J Traumatol, 2016, 19(5): 259-263.
12	LIU Z, LI C W, MAO Y F, et al. Study on zoledronic acid reducing acute bone loss and fracture rates in elderly postoperative patients with intertrochanteric fractures[J]. Orthop Surg, 2019, 11(3): 380-385.
13	LYLES K W, COLÓN-EMERIC C S, MAGAZINER J S, et al. Zoledronic acid and clinical fractures and mortality after hip fracture[J]. N Engl J Med, 2007, 357(18): 1799-1809.
14	朱佳福, 徐卫星, 刘宏. InterTan髓内钉治疗老年股骨转子间冠状位骨折的病例对照研究[J]. 中国骨伤, 2016, 29(12): 1130-1134.
	ZHU J F, XU W X, LIU H. Case-control study on InterTan intramedullary nail in treating coronal femoral intertrochanteric fracture in elderly[J]. China Journal of Orthopaedics and Traumatology, 2016, 29(12): 1130-1134.
15	王武, 翟生, 韩小平, 等. 股骨近端抗旋髓内钉与动力髋螺钉对老年不稳定股骨粗隆间骨折疗效的对比研究[J]. 中华医学杂志, 2018, 98(5): 357-361.
	WANG W, ZHAI S, HAN X P, et al. Comparative study of proximal femoral nail anti-rotation and dynamic hip screw in the unstable intertrochanteric fractures in the elderly[J]. National Medical Journal of China, 2018, 98(5): 357-361.
16	BAUMGAERTNER M R, CURTIN S L, LINDSKOG D M. Intramedullary versus extramedullary fixation for the treatment of intertrochanteric hip fractures[J]. Clin Orthop Relat Res, 1998(348): 87-94.
17	KOVAL K J, SKOVRON M L, AHARONOFF G B, et al. Ambulatory ability after hip fracture. A prospective study in geriatric patients[J]. Clin Orthop Relat Res, 1995(310): 150-159.
18	GANZER D, FORKE L, IRLENBUSCH U. Two-year follow-up of revision total hip arthroplasty using a ceramic revision head with a retained well-fixed femoral component: a case series[J]. J Med Case Rep, 2014, 8: 434.
19	中华医学会骨质疏松和骨矿盐疾病分会. 原发性骨质疏松症诊疗指南(2022)[J]. 中国全科医学, 2023, 26(14): 1671-1691.
	Chinese Society of Osteoporosis and Bone Mineral Research. Guidelines for the diagnosis and treatment of primary osteoporosis (2022)[J]. Chinese General Practice, 2023, 26(14): 1671-1691.
20	QASEEM A, HICKS L A, ETXEANDIA-IKOBALTZETA I, et al. Pharmacologic treatment of primary osteoporosis or low bone mass to prevent fractures in adults: a living clinical guideline from the American College of Physicians[J]. Ann Intern Med, 2023, 176(2): 224-238.
21	SCHINDELER A, MCDONALD M M, BOKKO P, et al. Bone remodeling during fracture repair: the cellular picture[J]. Semin Cell Dev Biol, 2008, 19(5): 459-466.
22	BAIMA FILHO F A S, MENDONÇA P G, SILVA G E B, et al. The analysis of alendronate action in bone fracture healing in rats[J]. J Clin Orthop Trauma, 2020, 11(Suppl 5): S856-S860.
23	KIDD L J, COWLING N R, WU A C, et al. Bisphosphonate treatment delays stress fracture remodeling in the rat ulna[J]. J Orthop Res, 2011, 29(12): 1827-1833.
24	SOLOMON D H, HOCHBERG M C, MOGUN H, et al. The relation between bisphosphonate use and non-union of fractures of the humerus in older adults[J]. Osteoporos Int, 2009, 20(6): 895-901.
25	DUCKWORTH A D, MCQUEEN M M, TUCK C E, et al. Effect of alendronic acid on fracture healing: a multicenter randomized placebo-controlled trial[J]. J Bone Miner Res, 2019, 34(6): 1025-1032.
26	COLÓN-EMERIC C, NORDSLETTEN L, OLSON S, et al. Association between timing of zoledronic acid infusion and hip fracture healing[J]. Osteoporos Int, 2011, 22(8): 2329-2336.
27	ZHOU W, LIU Y, GUO X, et al. Effects of zoledronic acid on bone mineral density around prostheses and bone metabolism markers after primary total hip arthroplasty in females with postmenopausal osteoporosis[J]. Osteoporos Int, 2019, 30(8): 1581-1589.
28	GULIA A, DAS S P, SONDUR S, et al. Zoledronic acid does not retard bone union: a randomized controlled trial in fragility intertrochanteric femur fractures[J]. Cureus, 2023, 15(1): e33948.
29	DING Q R, CHEN J, FAN J, et al. Effect of zoledronic acid on lumbar spinal fusion in osteoporotic patients[J]. Eur Spine J, 2017, 26(11): 2969-2977.
30	虞慧婷, 夏天, 王春芳, 等. 上海市居民期望寿命与健康期望寿命的差异分析[J]. 中华流行病学杂志, 2021, 42(6): 1018-1023.
	YU H T, XIA T, WANG C F, et al. Analysis on the difference between life expectancy and healthy life expectancy in Shanghai[J]. Chinese Journal of Epidemiology, 2021, 42(6): 1018-1023.
31	ROSSO F, DETTONI F, BONASIA D E, et al. Prognostic factors for mortality after hip fracture: operation within 48 hours is mandatory[J]. Injury, 2016, 47(Suppl 4): S91-S97.
32	WANG P W, YAO X D, ZHUANG H F, et al. Mortality and related risk factors of fragile hip fracture[J]. Orthop Surg, 2022, 14(10): 2462-2469.
33	PAN L P, NING T G, WU H, et al. Prognostic nomogram for risk of mortality after hip fracture surgery in geriatrics[J]. Injury, 2022, 53(4): 1484-1489.
34	《中国老年骨质疏松症诊疗指南(2023)》工作组, 中国老年学和老年医学学会骨质疏松分会, 中国医疗保健国际交流促进会骨质疏松病学分会, 等. 中国老年骨质疏松症诊疗指南(2023)[J]. 中华骨与关节外科杂志, 2023, 16(10): 865-885.
	Workgroup of Chinese Guideline for the Diagnosis and Treatment of Senile Osteoporosis (2023), Osteoporosis Society of China Association of Gerontology and Geriatrics, Osteporosis Society of China International Exchange and Promotive Association for Medical and Health Care, et al. China guideline for diagnosis and treatment of senile osteoporosis (2023)[J]. Chinese Journal of Bone and Joint Surgery, 2023, 16(10): 865-885.
35	ESPINOSA K A, GÉLVEZ A G, TORRES L P, et al. Pre-operative factors associated with increased mortality in elderly patients with a hip fracture: a cohort study in a developing country[J]. Injury, 2018, 49(6): 1162-1168.
36	KREGOR P J, OBREMSKEY W T, KREDER H J, et al. Unstable pertrochanteric femoral fractures[J]. J Orthop Trauma, 2014, 28(Suppl 8): S25-S28.
37	SPRAGUE S, SCHEMITSCH E H, SWIONTKOWSKI M, et al. Factors associated with revision surgery after internal fixation of hip fractures[J]. J Orthop Trauma, 2018, 32(5): 223-230.
38	SANZ-REIG J, MARÍN J S, PÉREZ ALBA J M, et al. Risk factors for in-hospital mortality following hip fracture[J]. Rev Esp Cir Ortop Traumatol, 2017, 61(4): 209-215.
39	VAN DER SIJP M P L, VAN EIJK M, NIGGEBRUGGE A H P, et al. Prognostic factors for short-term recovery of independence in a multistate model for patients with a hip fracture[J]. J Am Med Dir Assoc, 2021, 22(6): 1307-1312.

Characteristic	Before PSM (n=174)			After PSM (n=90)
Characteristic	ZA group (n=26)	Control group (n=148)	P value	ZA group (n=25)	Control group (n=65)	P value
Age/year	83.5 (80.8, 87.2)	87.0 (84.0, 90.0)	0.002	84.0 (81.0, 87.0)	85.0 (82.0, 87.5)	0.418
Gender/n(%)			0.438			0.952
Male	18 (69.2)	113 (76.4)		18 (72.0)	49 (75.4)
Female	8 (30.8)	35 (23.6)		7 (28.0)	16 (24.6)
BMI/(kg·m^-2)	21.9 (18.9, 24.0)	21.3 (18.7, 23.4)	0.893	21.8 (18.9, 23.9)	20.8 (18.3, 23.4)	0.975
Fracture classification/n(%)			0.299			1.000
Stable fracture	19 (73.1)	124 (83.8)		19 (76.0)	50 (76.9)
Unstable fracture	7 (26.9)	24 (16.2)		6 (24.0)	15 (23.1)
Multiple fractures/n(%)			0.785			0.973
Yes	5 (19.2)	22 (14.9)		5 (20.0)	11 (16.9)
No	21 (80.8)	126 (85.1)		20 (80.0)	54 (83.1)
Surgical reduction/n(%)			0.103			0.101
Good	15 (57.7)	60 (40.5)		14 (56.0)	24 (36.9)
Acceptable	11 (42.3)	88 (59.5)		11 (44.0)	41 (63.1)
Bone density/n(%)			0.071			0.285
Osteoporosis	18 (69.2)	127 (85.8)		18 (72.0)	55 (84.6)
Osteopenia	8 (30.8)	21 (14.2)		7 (28.0)	10 (15.4)
Diabetes/n(%)			0.315			0.178
Yes	8 (30.8)	61 (41.2)		8 (32.0)	31 (47.7)
No	18 (69.2)	87 (58.8)		17 (68.0)	34 (52.3)
Cardio-cerebral vascular events/n(%)			0.671			0.371
Yes	12 (46.2)	75 (50.7)		12 (48.0)	38 (58.5)
No	14 (53.8)	73 (49.3)		13 (52.0)	27 (41.5)
LLDVT/n(%)			0.891			0.543
Yes	6 (23.1)	36 (24.3)		5 (20.0)	17 (26.2)
No	20 (76.9)	112 (75.7)		20 (80.0)	48 (73.8)
Hb/(g·L^-1)	111.5 (97.5, 120.8)	103.5 (89.0, 117.8)	0.100	112.0 (96.0, 121.5)	108.0 (87.0, 121.0)	0.322
Alb/(g·L^-1)	34.5 (32.8, 37.3)	34.0 (31.0, 36.0)	0.071	35.0 (33.0, 37.5)	35.0 (32.0, 36.5)	0.198

Characteristic	Before PSM (n=174)			After PSM (n=90)
Characteristic	ZA group (n=26)	Control group (n=148)	P value	ZA group (n=25)	Control group (n=65)	P value
Age/year	83.5 (80.8, 87.2)	87.0 (84.0, 90.0)	0.002	84.0 (81.0, 87.0)	85.0 (82.0, 87.5)	0.418
Gender/n(%)			0.438			0.952
Male	18 (69.2)	113 (76.4)		18 (72.0)	49 (75.4)
Female	8 (30.8)	35 (23.6)		7 (28.0)	16 (24.6)
BMI/(kg·m^-2)	21.9 (18.9, 24.0)	21.3 (18.7, 23.4)	0.893	21.8 (18.9, 23.9)	20.8 (18.3, 23.4)	0.975
Fracture classification/n(%)			0.299			1.000
Stable fracture	19 (73.1)	124 (83.8)		19 (76.0)	50 (76.9)
Unstable fracture	7 (26.9)	24 (16.2)		6 (24.0)	15 (23.1)
Multiple fractures/n(%)			0.785			0.973
Yes	5 (19.2)	22 (14.9)		5 (20.0)	11 (16.9)
No	21 (80.8)	126 (85.1)		20 (80.0)	54 (83.1)
Surgical reduction/n(%)			0.103			0.101
Good	15 (57.7)	60 (40.5)		14 (56.0)	24 (36.9)
Acceptable	11 (42.3)	88 (59.5)		11 (44.0)	41 (63.1)
Bone density/n(%)			0.071			0.285
Osteoporosis	18 (69.2)	127 (85.8)		18 (72.0)	55 (84.6)
Osteopenia	8 (30.8)	21 (14.2)		7 (28.0)	10 (15.4)
Diabetes/n(%)			0.315			0.178
Yes	8 (30.8)	61 (41.2)		8 (32.0)	31 (47.7)
No	18 (69.2)	87 (58.8)		17 (68.0)	34 (52.3)
Cardio-cerebral vascular events/n(%)			0.671			0.371
Yes	12 (46.2)	75 (50.7)		12 (48.0)	38 (58.5)
No	14 (53.8)	73 (49.3)		13 (52.0)	27 (41.5)
LLDVT/n(%)			0.891			0.543
Yes	6 (23.1)	36 (24.3)		5 (20.0)	17 (26.2)
No	20 (76.9)	112 (75.7)		20 (80.0)	48 (73.8)
Hb/(g·L^-1)	111.5 (97.5, 120.8)	103.5 (89.0, 117.8)	0.100	112.0 (96.0, 121.5)	108.0 (87.0, 121.0)	0.322
Alb/(g·L^-1)	34.5 (32.8, 37.3)	34.0 (31.0, 36.0)	0.071	35.0 (33.0, 37.5)	35.0 (32.0, 36.5)	0.198

Follow-up index	Before PSM (n=174)			After PSM (n=90)
Follow-up index	ZA group (n=26)	Control group (n=148)	P value	ZA group (n=25)	Control group (n=65)	P value
Healed 6 weeks after surgery/n(%)			0.000			0.030
Yes	4 (15.4)	1 (0.7)		4 (16.0)	1 (1.5)
No	22 (84.6)	147 (99.3)		21 (84.0)	64 (98.5)
Healed 12 weeks after surgery/n(%)			0.022			0.019
Yes	25 (96.2)	113 (76.4)		24 (96.0)	48 (73.8)
No	1 (3.8)	35 (23.6)		1 (4.0)	17 (26.2)
Household ambulatory ability 6 weeks after surgery/n(%)			0.015			0.074
Yes	21 (80.8)	82 (55.4)		20 (80.0)	39 (60.0)
No	5 (19.2)	66 (44.6)		5 (20.0)	26 (40.0)
Harris score 12 weeks after surgery/point	86.0 (82.0, 91.0)	81.0 (75.3, 88.0)	0.001	86.0 (82.0, 91.0)	82.0 (77.0, 88.0)	0.019

Follow-up index	Before PSM (n=174)			After PSM (n=90)
Follow-up index	ZA group (n=26)	Control group (n=148)	P value	ZA group (n=25)	Control group (n=65)	P value
Healed 6 weeks after surgery/n(%)			0.000			0.030
Yes	4 (15.4)	1 (0.7)		4 (16.0)	1 (1.5)
No	22 (84.6)	147 (99.3)		21 (84.0)	64 (98.5)
Healed 12 weeks after surgery/n(%)			0.022			0.019
Yes	25 (96.2)	113 (76.4)		24 (96.0)	48 (73.8)
No	1 (3.8)	35 (23.6)		1 (4.0)	17 (26.2)
Household ambulatory ability 6 weeks after surgery/n(%)			0.015			0.074
Yes	21 (80.8)	82 (55.4)		20 (80.0)	39 (60.0)
No	5 (19.2)	66 (44.6)		5 (20.0)	26 (40.0)
Harris score 12 weeks after surgery/point	86.0 (82.0, 91.0)	81.0 (75.3, 88.0)	0.001	86.0 (82.0, 91.0)	82.0 (77.0, 88.0)	0.019

Factor	OR	95%CI	P value
Gender (male vs female)	1.46	0.59‒3.63	0.412
Age	0.96	0.88‒1.04	0.310
BMI	1.02	0.94‒1.12	0.584
Fracture classification (unstable vs stable)	0.09	0.04‒0.21	0.000
Multiple fractures (yes vs no)	1.60	0.52‒4.96	0.420
Surgical reduction (good vs acceptable)	19.09	4.41‒82.60	0.000
Bone density (osteoporosis vs osteopenia)	1.00	0.37‒2.68	1.000
Diabetes (yes vs no)	0.90	0.43‒1.90	0.900
Cardio-cerebral vascular events (yes vs no)	1.00	0.48‒2.08	1.000
LLDVT (yes vs no)	1.14	0.48‒2.75	0.763
Hb	1.02	1.00‒1.04	0.049
Alb	1.13	1.04‒1.24	0.004
Use of zoledronic acid (yes vs no)	7.74	1.01‒59.22	0.049