Effect of long-term use of proton pump inhibitors on bone mineral density and bone metabolism: a Meta-analysis

doi:10.3969/j.issn.2095-4344.3155

Abstract

Abstract: BACKGROUND: Proton pump inhibitors (PPI) are often used for the clinical treatment of gastroxia, and the long-term use of PPI can lead to osteoporosis. However, their relationship and mechanism are not yet clear. This systematic review aimed to clarify the relationship between the long-term use of PPI and osteoporosis from the perspective of bone mineral density (BMD) and bone metabolism.
METHODS: A search of CNKI, CBM, VIP, WanFang, PubMed, Web of Science, EMBASE, and Cochrane Library was performed using the main keywords of “osteoporosis; bone metabolism; proton pump inhibitor; PPI” in Chinese and English, respectively. The search time was from inception until March 1, 2020. Literature about the effect of long-term use of PPI on BMD and bone metabolism were retrieved and strictly assessed for literature quality. Relevant information and data were accurately extracted from the literature. The meta-analysis was performed using RevMan5.3.
RESULTS: A total of 9 studies involving 1 236 individuals were included. Meta-analysis results showed that: the BMD of the lumbar L1-4, femoral neck, and proximal femur as well as the overall BMD of the hip joint in the PPI group were significantly lower than those in the control group. Lumbar vertebra BMD: expressed as T value, mean difference (MD)=-0.24, 95% confidence interval (CI):-0.45 to-0.04, P=0.02, and expressed in g/cm2, MD=-0.12, 95%CI:-0.22 to -0.03, P=0.010); femoral neck BMD: MD=-0.31, 95%CI: -0.44 to -0.18, P < 0.000 01); proximal femoral BMD: MD=-0.17, 95%CI:-0.20 to-0.14, P < 0.000 01; overall BMD of the hip joint: MD=-0.27, 95%CI: -0.51 to -0.02, P=0.04. The level of osteocalcin in the PPI group was significantly higher than that in the control group (MD=0.23, 95%CI: 0.19-0.27, P < 0.000 01). The level of parathyroid hormone in the PPI group was lower than that in the control group, and the difference was not statistically significant (MD=-0.19, 95%CI: -1.91 to 1.53, P=0.83). In conclusion, the long-term use of PPI can reduce BMD and increase osteocalcin level, which easily lead to osteoporosis but the effects on parathyroid hormone level is yet unknown. Further high-quality studies are required to verify the above conclusions.

Key words: , bone, hip, femur, lumbar vertebra, osteocalcin, parathyroid hormone, bone mineral density, bone metabolism, Meta-analysis

CLC Number:

Chen Jiayun, Li Anan, Lü Zhaohui, Wu Zixuan, Cai Minjie, Huang Xuyan . Effect of long-term use of proton pump inhibitors on bone mineral density and bone metabolism: a Meta-analysis[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(17): 2775-2780.

Figures/Tables 5

腰椎骨密度：以T值统计腰椎骨密度的文献共有5篇[14-17，20]，以g/cm2为单位统计骨密度的文献共有4篇[12-13，18-19]。以 T 值统计腰椎骨密度的5篇文献[14-17，20]，异质性分析 P=0.89，I2=0%，在固定效应模型下，分析结果表明PPI组腰椎骨密度低于对照组(MD=-0.24，95%CI：-0.45至 -0.04，P=0.02)。以g/cm2为单位统计腰椎骨密度的4篇文献[12-13，18-19]，异质性分析：P < 0.000 01，I2=93%，在随机效应模型下，分析结果表明PPI组腰椎骨密度低于对照组(MD=-0.12，95%CI：-0.22至-0.03，P=0.010)。此异质性较大，研究间无法查明临床上或方法学上的异质性来源，故采用描述性定性分析：有4篇文献结果均表明 PPI 组腰椎骨密度低于对照组(P < 0.05)[12-13，18-19]。股骨颈骨密度：有6篇文献报道了长期服用 PPI 对股骨颈骨密度的影响[12，14-17，20]，其中5篇文献以 T 值统计[14-17，20]，1 篇文献以 g/cm2 为单位统计[12]。对以 T 值统计骨密度的5篇文献进行Meta分析[14-17，20]，异质性分析：P=0.11，I2=47%，在固定效应模型下，分析结果表明PPI 组股骨颈骨密度低于对照组(MD=-0.31，95%CI：-0.44至-0.18，P < 0.000 01)。对以g/cm2为单位统计骨密度的1篇文献进行描述性定性分析[12]：该文献结果认为 PPI组股骨颈骨密度低于对照组(P < 0.05)。股骨近端骨密度：由3篇文献报道了长期服用 PPI 对股骨近端骨密度的影响[13，18-19]，异质性分析 P=0.30，I2=17%，在固定效应模型下，分析结果表明 PPI 组股骨近端骨密度低于对照组(MD=-0.17，95%CI：-0.20至-0.14，P < 0.000 01)。髋关节总体骨密度：有4篇文献报道了长期服用 PPI 对髋关节骨密度的影响[14-15，17，20]，异质性分析：P=0.05，I2=61%，在随机效应模型下，分析结果表明PPI组髋关节总体骨密度低于对照组(MD=-0.27，95%CI：-0.51至-0.02，P=0.04)。此异质性稍大，通过观察，其中有2篇文献研究对象为白种人[17， 20]，2篇文献研究对象为黄种人[14-15]，因此，将其分为2组进行分析时，发现各自的异质性均降至0%，异质性检测结果分别为：白种人：P=0.83，I2=0%；黄种人：P=0.97，I2=0%。可见，人种差异可能是异质性的来源。 2.3.2 各组骨钙素差异纳入的文献中有4篇文献报道了长期服用 PPI 对骨钙素的影响[12，17-19]，共340例患者，其中PPI组168例，对照组172 例。异质性分析：P=0.96，I2=0%，在固定效应模型下，分析结果表明 PPI 组骨钙素高于对照组(MD=0.23，95%CI：0.19-0.27，P < 0.000 01)，如图4。 "

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