抗骨质疏松症药物对糖尿病患者糖代谢及骨代谢的影响
|
摘要
糖尿病是骨质疏松性骨折的危险因素之一,无论是1型还是2型糖尿病患者,其发生骨质疏松症和糖尿病性骨折的风险均显著升高。研究表明,糖尿病患者骨转换指标明显低于正常人群,尤其是骨形成动力不足。目前针对糖尿病合并骨质疏松症患者的抗骨质疏松治疗尚无明确的指南。抗骨质疏松症药物尤其是抗骨吸收药物,可进一步降低骨转换,同时,其可能影响骨钙素(osteocalcin,OC)等细胞因子的分泌从而对糖代谢产生不利影响。而目前许多动物实验及临床研究发现,常用抗骨质疏松症药物用于糖尿病患者不仅有抗骨质疏松作用,甚至可能对糖代谢产生积极影响。本文通过综述抗骨质疏松症药物对糖尿病患者糖代谢及骨代谢的影响,旨在为糖尿病患者抗骨质疏松治疗及避免糖尿病性骨折的发生提供有效的参考。
Diabetes is one of the risk factors of osteoporotic fractures, and there is a significant increase in the risk of osteoporotic and diabetic fractures in patients with type 1 and type 2 diabetes. Studies have shown that the bone turnover in diabetic patients is significantly lower than that in the normal population, especially in terms of bone formation dynamics. There is no clear guidance for the treatment of osteoporosis in patients with diabetes and osteoporosis. Anti-osteoporotic drugs, particularly anti-resorptive drugs can further reduce bone turnover, and affect the secretion of cytokines such as osteocalcin, which may adversely affect glucose metabolism. Currently, many animal experiments and clinical studies have found that commonly used anti-osteoporotic drugs in diabetic patients not only have anti-osteoporosis effects but also have a positive effect on glucose metabolism. This article reviews the effects of anti-osteoporotic drugs on glucose metabolism and bone metabolism in diabetic patients, and hopes to provide an effective reference for the anti-osteoporotic treatment in diabetic patients and to avoid the occurrence of diabetic fractures.
Diabetes is one of the risk factors of osteoporotic fractures, and there is a significant increase in the risk of osteoporotic and diabetic fractures in patients with type 1 and type 2 diabetes. Studies have shown that the bone turnover in diabetic patients is significantly lower than that in the normal population, especially in terms of bone formation dynamics. There is no clear guidance for the treatment of osteoporosis in patients with diabetes and osteoporosis. Anti-osteoporotic drugs, particularly anti-resorptive drugs can further reduce bone turnover, and affect the secretion of cytokines such as osteocalcin, which may adversely affect glucose metabolism. Currently, many animal experiments and clinical studies have found that commonly used anti-osteoporotic drugs in diabetic patients not only have anti-osteoporosis effects but also have a positive effect on glucose metabolism. This article reviews the effects of anti-osteoporotic drugs on glucose metabolism and bone metabolism in diabetic patients, and hopes to provide an effective reference for the anti-osteoporotic treatment in diabetic patients and to avoid the occurrence of diabetic fractures.
引文
[1] Starup-Linde J,Vestergaard P.Biochemical bone turnover markers in diabetes mellitus-A systematic review[J].Bone,2016,82:69-78.
[2] Hygum K,Starup-Linde J,Harsl?f T,et al.Mechanisms in endocrinology:Diabetes mellitus,a state of low bone turnover-a systematic review and meta-analysis[J].European Journal of Endocrinology,2017,176(3):R137.
[3] Fernandes TAP,Gon?alves LML,Brito JAA.Relationships between bone turnover and energy metabolism[J].Journal of Diabetes Research,2017,2017(3):1-11.
[4] Kunutsor SK,Apekey TA,Laukkanen JA.Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes:systematic review and meta-analysis of observational evidence[J].European Journal of Epidemiology,2015,30(8):599-614.
[5] Lindsey RC,Mohan S.Skeletal effects of growth hormone and insulin-like growth factor-I therapy[J].Molecular & Cellular Endocrinology,2016,432(C):44-55.
[6] Miyake H,Kanazawa I,Sugimoto T.Decreased serum Insulin-like growth factor-I is a risk factor for non-vertebral fractures in diabetic postmenopausal women[J].Internal Medicine,2017,56(3):269-273.
[7] Hong S,Koo J,Jin KH,et al.Changes in serum osteocalcin are not associated with changes in glucose or insulin for osteoporotic patients treated with bisphosphonate[J].Journal of Bone Metabolism,2013,20(1):37-41.
[8] Coe LM,Tekalur SA,Shu Y,et al.Bisphosphonate treatment of type I diabetic mice prevents early bone loss but accentuates suppression of bone formation[J].Journal of Cellular Physiology,2015,230(8):1944-1953.
[9] Keegan TH,Schwartz AV,Bauer DC,et al.Effect of alendronate on bone mineral density and biochemical markers of bone turnover in type 2 diabetic women:the fracture intervention trial[J].Diabetes Care,2004,27(7):1547.
[10] Inoue D,Muraoka R,Okazaki R,et al.Efficacy and safety of risedronate in osteoporosis subjects with comorbid diabetes,hypertension,and/or dyslipidemia:A post hoc analysis of phase III trials conducted in Japan[J].Calcif Tissue Int,2016,98(2):114-122.
[11] Iwamoto Jun,Sato Yoshihiro,Uzawa Mitsuyoshi,et al.Three-year experience with alendronate treatment in postmenopausal osteoporotic Japanese women with or without renal dysfunction:a retrospective study[J].Drugs Aging,2012,29(2):133-142.
[12] Vestergaard P.Risk of newly diagnosed type 2 diabetes is reduced in users of alendronate.[J].Calcified Tissue International,2011,89(4):265-270.
[13] Abrahamsen B,Rubin KH,Eiken PA,et al.Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment:a National Prescription registry study[J].Osteoporosis International,2013,24(1):321-328.
[14] Chan DC,Yang RS,Ho CH,et al.The use of alendronate is associated with a decreased incidence of type 2 diabetes mellitus—A population-based cohort study in Taiwan[J].PLoS One,2015,10(4):e0123279.
[15] Dexue L,Yueyue Z.Salmon calcitonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis[J].Pakistan Journal of Pharmaceutical Sciences,2014,27(6 Suppl):2079-2081.
[16] 包勤文,申潇竹,龚晨,等.鲑鱼降钙素联合依帕司他对老年2型糖尿病伴骨质疏松患者周围神经病变疼痛的疗效观察[J].中国骨质疏松杂志,2016,22(5):588-591.
[17] Lee SM,Hay DL,Pioszak AA.Calcitonin and amylin receptor peptide interaction mechanisms:Insights into peptide-binding modes and allosteric modulation of the calcitonin receptor by receptor activity-modifying proteins[J].Journal of Biological Chemistry,2016,291(16):8686.
[18] Feigh M,Hjuler ST,Andreassen KV,et al.Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats[J].European Journal of Pharmacology,2014,737(4):91-96.
[19] Xu B,Lovre D,Mauvaisjarvis F.The effect of selective estrogen receptor modulators on type 2 diabetes onset in women:Basic and clinical insights[J].J Diabetes Complications,2017,31(4):773-779.
[20] Mori H,Okada Y,Kishikawa H,et al.Effects of raloxifene on lipid and bone metabolism in postmenopausal women with type 2 diabetes[J].Journal of Bone & Mineral Metabolism,2013,31(1):89-95.
[21] Sato M,Ye W,Sugihara T,et al.Fracture risk and healthcare resource utilization and costs among osteoporosis patients with type 2 diabetes mellitus and without diabetes mellitus in Japan:retrospective analysis of a hospital claims database[J].BMC Musculoskeletal Disorders,2016,17(1):489.
[22] Johnell O,John A,Kanis MD,et al.Associations between baseline risk factors and vertebral fracture risk in the multiple outcomes of raloxifene evaluation (MORE) study[J].J Bone Miner Res,2010,19(5):764-772.
[23] Ensrud KE,Stock JL,Barrett-Connor E,et al.Effects of raloxifene on fracture risk in postmenopausal women:the Raloxifene Use for the Heart Trial[J].J Bone Miner Res,2010,23(1):112-120.
[24] Xu B,Lovre D,Mauvais-Jarvis F.Effect of selective estrogen receptor modulators on metabolic homeostasis[J].Biochimie,2016,124:92-97.
[25] Lasco A,Gaudio A,Morabito N,et al.Effects of a long-term treatment with raloxifene on insulin sensitivity in postmenopausal women[J].Diabetologia,2004,47(3):571-574.
[26] Kiechl S,Wittmann J,Giaccari A,et al.Blockade of receptor activator of nuclear factor-[kappa]B (RANKL) signaling improves hepatic insulin resistance and prevents development of diabetes mellitus[J].Nature Medicine,2013,19(3):358-363.
[27] Lasco A,Morabito N,Basile G,et al.Denosumab inhibition of RANKL and insulin resistance in postmenopausal women with osteoporosis[J].Calcified Tissue International,2016,98(2):123-128.
[28] Napoli N,Pannacciulli N,Vittinghoff E,et al.Effect of denosumab on fasting glucose in women with diabetes or prediabetes from the freedom trial[J].Diabetes Metab Res Rev,2018,34(4):e2991.
[29] Yamamoto M,Yamaguchi T,Nawata K,et al.Decreased PTH levels accompanied by low bone formation are associated with vertebral fractures in postmenopausal women with type 2 diabetes[J].J Clin Endocrinol Metab,2012,97(4):1277-1284.
[30] Motyl KJ,Mccauley LK,Mccabe LR.Amelioration of type I diabetes-induced osteoporosis by parathyroid hormone is associated with improved osteoblast survival[J].Journal of Cellular Physiology,2012,227(4):1326-1334.
[31] Hamann C,Picke AK,Campbell GM,et al.Effects of parathyroid hormone on bone mass,bone strength,and bone regeneration in male rats with type 2 diabetes mellitus[J].Endocrinology,2014,155(4):1197-1206.
[32] Rybaczek T,Tangl S,Dobsak T,et al.The effect of parathyroid hormone on osseointegration in insulin-treated diabetic rats[J].Implant Dentistry,2015,24(4):392.
[33] Schwartz AV,Pavo I,Alam J,et al.Teriparatide in patients with osteoporosis and type 2 diabetes[J].Bone,2016,91:152-158.
[2] Hygum K,Starup-Linde J,Harsl?f T,et al.Mechanisms in endocrinology:Diabetes mellitus,a state of low bone turnover-a systematic review and meta-analysis[J].European Journal of Endocrinology,2017,176(3):R137.
[3] Fernandes TAP,Gon?alves LML,Brito JAA.Relationships between bone turnover and energy metabolism[J].Journal of Diabetes Research,2017,2017(3):1-11.
[4] Kunutsor SK,Apekey TA,Laukkanen JA.Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes:systematic review and meta-analysis of observational evidence[J].European Journal of Epidemiology,2015,30(8):599-614.
[5] Lindsey RC,Mohan S.Skeletal effects of growth hormone and insulin-like growth factor-I therapy[J].Molecular & Cellular Endocrinology,2016,432(C):44-55.
[6] Miyake H,Kanazawa I,Sugimoto T.Decreased serum Insulin-like growth factor-I is a risk factor for non-vertebral fractures in diabetic postmenopausal women[J].Internal Medicine,2017,56(3):269-273.
[7] Hong S,Koo J,Jin KH,et al.Changes in serum osteocalcin are not associated with changes in glucose or insulin for osteoporotic patients treated with bisphosphonate[J].Journal of Bone Metabolism,2013,20(1):37-41.
[8] Coe LM,Tekalur SA,Shu Y,et al.Bisphosphonate treatment of type I diabetic mice prevents early bone loss but accentuates suppression of bone formation[J].Journal of Cellular Physiology,2015,230(8):1944-1953.
[9] Keegan TH,Schwartz AV,Bauer DC,et al.Effect of alendronate on bone mineral density and biochemical markers of bone turnover in type 2 diabetic women:the fracture intervention trial[J].Diabetes Care,2004,27(7):1547.
[10] Inoue D,Muraoka R,Okazaki R,et al.Efficacy and safety of risedronate in osteoporosis subjects with comorbid diabetes,hypertension,and/or dyslipidemia:A post hoc analysis of phase III trials conducted in Japan[J].Calcif Tissue Int,2016,98(2):114-122.
[11] Iwamoto Jun,Sato Yoshihiro,Uzawa Mitsuyoshi,et al.Three-year experience with alendronate treatment in postmenopausal osteoporotic Japanese women with or without renal dysfunction:a retrospective study[J].Drugs Aging,2012,29(2):133-142.
[12] Vestergaard P.Risk of newly diagnosed type 2 diabetes is reduced in users of alendronate.[J].Calcified Tissue International,2011,89(4):265-270.
[13] Abrahamsen B,Rubin KH,Eiken PA,et al.Characteristics of patients who suffer major osteoporotic fractures despite adhering to alendronate treatment:a National Prescription registry study[J].Osteoporosis International,2013,24(1):321-328.
[14] Chan DC,Yang RS,Ho CH,et al.The use of alendronate is associated with a decreased incidence of type 2 diabetes mellitus—A population-based cohort study in Taiwan[J].PLoS One,2015,10(4):e0123279.
[15] Dexue L,Yueyue Z.Salmon calcitonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis[J].Pakistan Journal of Pharmaceutical Sciences,2014,27(6 Suppl):2079-2081.
[16] 包勤文,申潇竹,龚晨,等.鲑鱼降钙素联合依帕司他对老年2型糖尿病伴骨质疏松患者周围神经病变疼痛的疗效观察[J].中国骨质疏松杂志,2016,22(5):588-591.
[17] Lee SM,Hay DL,Pioszak AA.Calcitonin and amylin receptor peptide interaction mechanisms:Insights into peptide-binding modes and allosteric modulation of the calcitonin receptor by receptor activity-modifying proteins[J].Journal of Biological Chemistry,2016,291(16):8686.
[18] Feigh M,Hjuler ST,Andreassen KV,et al.Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats[J].European Journal of Pharmacology,2014,737(4):91-96.
[19] Xu B,Lovre D,Mauvaisjarvis F.The effect of selective estrogen receptor modulators on type 2 diabetes onset in women:Basic and clinical insights[J].J Diabetes Complications,2017,31(4):773-779.
[20] Mori H,Okada Y,Kishikawa H,et al.Effects of raloxifene on lipid and bone metabolism in postmenopausal women with type 2 diabetes[J].Journal of Bone & Mineral Metabolism,2013,31(1):89-95.
[21] Sato M,Ye W,Sugihara T,et al.Fracture risk and healthcare resource utilization and costs among osteoporosis patients with type 2 diabetes mellitus and without diabetes mellitus in Japan:retrospective analysis of a hospital claims database[J].BMC Musculoskeletal Disorders,2016,17(1):489.
[22] Johnell O,John A,Kanis MD,et al.Associations between baseline risk factors and vertebral fracture risk in the multiple outcomes of raloxifene evaluation (MORE) study[J].J Bone Miner Res,2010,19(5):764-772.
[23] Ensrud KE,Stock JL,Barrett-Connor E,et al.Effects of raloxifene on fracture risk in postmenopausal women:the Raloxifene Use for the Heart Trial[J].J Bone Miner Res,2010,23(1):112-120.
[24] Xu B,Lovre D,Mauvais-Jarvis F.Effect of selective estrogen receptor modulators on metabolic homeostasis[J].Biochimie,2016,124:92-97.
[25] Lasco A,Gaudio A,Morabito N,et al.Effects of a long-term treatment with raloxifene on insulin sensitivity in postmenopausal women[J].Diabetologia,2004,47(3):571-574.
[26] Kiechl S,Wittmann J,Giaccari A,et al.Blockade of receptor activator of nuclear factor-[kappa]B (RANKL) signaling improves hepatic insulin resistance and prevents development of diabetes mellitus[J].Nature Medicine,2013,19(3):358-363.
[27] Lasco A,Morabito N,Basile G,et al.Denosumab inhibition of RANKL and insulin resistance in postmenopausal women with osteoporosis[J].Calcified Tissue International,2016,98(2):123-128.
[28] Napoli N,Pannacciulli N,Vittinghoff E,et al.Effect of denosumab on fasting glucose in women with diabetes or prediabetes from the freedom trial[J].Diabetes Metab Res Rev,2018,34(4):e2991.
[29] Yamamoto M,Yamaguchi T,Nawata K,et al.Decreased PTH levels accompanied by low bone formation are associated with vertebral fractures in postmenopausal women with type 2 diabetes[J].J Clin Endocrinol Metab,2012,97(4):1277-1284.
[30] Motyl KJ,Mccauley LK,Mccabe LR.Amelioration of type I diabetes-induced osteoporosis by parathyroid hormone is associated with improved osteoblast survival[J].Journal of Cellular Physiology,2012,227(4):1326-1334.
[31] Hamann C,Picke AK,Campbell GM,et al.Effects of parathyroid hormone on bone mass,bone strength,and bone regeneration in male rats with type 2 diabetes mellitus[J].Endocrinology,2014,155(4):1197-1206.
[32] Rybaczek T,Tangl S,Dobsak T,et al.The effect of parathyroid hormone on osseointegration in insulin-treated diabetic rats[J].Implant Dentistry,2015,24(4):392.
[33] Schwartz AV,Pavo I,Alam J,et al.Teriparatide in patients with osteoporosis and type 2 diabetes[J].Bone,2016,91:152-158.