Clin Osteol 2020; 25(3): 107-114

How to treat a diabetic patient with osteoporosisReview articles

Jackuliak Peter; Kovářová Magdaléna; Kužma Martin; Killinger Zdenko; Payer Juraj
V. interná klinika LF UK a UNB, Nemocnica Ružinov, Bratislava

Diabetes mellitus and osteoporosis are two serious civilization diseases with increasing incidence. Osteoporosis and osteoporotic fractures are already accepted as a severe co-morbidity and complications of diabetes mellitus. In management of diabetic patients is necessary to identify the high-risk group for osteoporosis and fractures, and to take appropriate preventive and therapeutic options. Available antiresorptive and osteoanabolic drug agents, which are used to treat osteoporosis, are effective also in diabetes patients. Most of the data of their effects in dia­betics come only from clinical practice. But it is also necessary to achieve optimal glycaemic control, with regard to the effect of antidiabetics on bone. This review provides data from clinical studies on the effect of antiporotics in diabetics as well as the effect of antidiabetics on bone.

Keywords: antidiabetic therapy ; antiresorptive therapy ; diabetes mellitus ; osteoporotic fracture

Received: February 25, 2020; Accepted: March 23, 2020; Published: December 11, 2020  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Jackuliak P, Kovářová M, Kužma M, Killinger Z, Payer J. How to treat a diabetic patient with osteoporosis. Clinical Osteology. 2020;25(3):107-114.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Costantini S, Conte C. Bone health in diabetes and prediabetes. World J Diabetes 2019; 10(8): 421-445. Dostupné z DOI: <http://dx.doi.org/10.4239/wjd.v10.i8.421>. Go to original source...
    2. Shah VN, Shah CS, Snell-Bergeon JK. Type 1 diabetes and risk of fracture: meta-analysis and review of the literature. Diabet Med 2015; 32(9): 1134-1142. Dostupné z DOI: <http://dx.doi.org/10.1111/dme.12734>. Go to original source...
    3. Dhaliwal R, Foster NC, Boyle C et al. Determinants of fracture in adults with type 1 diabetes in the USA: Results from the T1D Exchange Clinic Registry. J Diabetes Complications 2018; 32(11): 1006-1011. Dostupné z DOI: <http://dx.doi.org/10.1016/j.jdiacomp.2018.08.016>. Go to original source...
    4. Vestergaard P, Rejnmark L, Mosekilde L. Relative fracture risk in patients with diabetes mellitus, and the impact of insulin and oral antidiabetic medication on relative fracture risk. Diabetologia 2005; 48(7): 1292-1299. Dostupné z DOI: <http://dx.doi.org/10.1007/s00125-005-1786-3>. Go to original source...
    5. Wang H, Ba Y, Xing Q, et al. Diabetes mellitus and the risk of fractures at specific sites: a meta-analysis. BMJ Open 2019; 9(1): e024067. Dostupné z DOI: <http://dx.doi.org/10.1136/bmjopen-2018-024067>. Go to original source...
    6. Moayeri A, Mohamadpour M, Mousavi SF et al. Fracture risk in patients with type 2 diabetes mellitus and possible risk factors: a systematic review and meta-analysis. Ther Clin Risk Manag 2017; 13 : 455-468. Dostupné z DOI: <http://dx.doi.org/10.2147/TCRM.S131945>. Go to original source...
    7. Maurer MS, Burcham J, Cheng H. Diabetes mellitus is associated with an increased risk of falls in elderly residents of a long-term care facility. J Gerontol A Biol Sci Med Sci 2005; 60(9): 1157-1162. Dostupné z DOI: <http://dx.doi.org/10.1093/gerona/60.9.1157>. Go to original source...
    8. Patel S, Hyer S, Tweed K et al. Risk factors for fractures and falls in older women with type 2 diabetes mellitus. Calcif Tissue Int 2008; 82(2): 87-91. Dostupné z DOI: <http://dx.doi.org/10.1007/s00223-007-9082-5>. Go to original source...
    9. Picke A-K, Campbell G, Napoli N et al. Update on the impact of type 2 diabetes mellitus on bone metabolism and material properties. Endocr Connect 2019; 8(3): R55-R70. Dostupné z DOI: <http://dx.doi.org/10.1530/EC-18-0456> Go to original source...
    10. [American Diabetes Association]. 4. Comprehensive Medical Evaluation and Assessment of Comorbidities: Standards of Medical Care in Diabetes 2020. Diabetes Care 2020; 43(Suppl 1): S37-S47. Dostupné z DOI: <http://dx.doi.org/10.2337/dc20-S004>. Go to original source...
    11. Cummings SR, Nevitt MC, Browner WS et al. Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 1995; 332(12): 767-773. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJM199503233321202>. Go to original source...
    12. Schwartz AV, Sellmeyer DE, Ensrudet KE al. Older women with diabetes have an increased risk of fracture: a prospective study. J Clin Endocrinol Metab 2001; 86(1): 32-38. Dostupné z DOI: <http://dx.doi.org/10.1210/jcem.86.1.7139>. Go to original source...
    13. Forsén L, Meyer HE, Midthjell K et al. Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trondelag Health Survey. Diabetologia 1999; 42(8): 920-925. Dostupné z DOI: <http://dx.doi.org/10.1007/s001250051248>. Go to original source...
    14. Michaelsson K, Holmberg L, Mallmin H et al. Diet and hip fracture risk: a case-control study. Study Group of the Multiple Risk Survey on Swedish Women for Eating Assessment. Int J Epidemiol 1995; 24(4): 771-782. Dostupné z DOI: <http://dx.doi.org/10.1093/ije/24.4.771>. Go to original source...
    15. Ferrari SL, Abrahamsen B, Napoli N et al. Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int 2018; 29(12): 2585-2596. Dostupné z DOI: <http://dx.doi.org/10.1007/s00198-018-4650-2>. Go to original source...
    16. Leslie WD, Aubry-Rozier B, Lamy O et al. TBS (trabecular bone score) and diabetes-related fracture risk. J Clin Endocrinol Metab 2013; 98(2): 602-609. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2012-3118>. Go to original source...
    17. Ebrahimpur M, Sharifi F, Nezhad FA et al. Effect of diabetes on BMD and TBS values as determinants of bone health in the elderly: Bushehr Elderly Health program. J Diabetes Metab Disord 2019; 18(1): 99-106. Dostupné z DOI: <http://dx.doi.org/10.1007/s40200-019-00395-1>. Go to original source...
    18. Jackuliak P, Kužma M, Killinger Z et al. Good long-term glycemic compensation is associated with better trabecular bone score in postmenopausal women with type 2 diabetes. Physiol Res 2019; 68(Suppl 2): S149-S156. Dostupné z DOI: <http://dx.doi.org/10.33549/physiolres.934304>. Go to original source...
    19. Schwartz AV, Vittinghoff E, Bauer DC et al. Association of BMD and FRAX score with risk of fracture in older adults with type 2 diabetes. JAMA 2011; 305(21): 2184-2192. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2011.715>. Go to original source...
    20. Leslie WD, Rubin MR, Schwartz AV et al. Type 2 diabetes and bone. J Bone Miner Res 2012; 27(11): 2231-2237. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.1759>. Go to original source...
    21. Giangregorio LM, Leslie WD, Lix LM et al. FRAX underestimates fracture risk in patients with diabetes. J Bone Miner Res 2012 : 27(2): 301-308. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.556>. Go to original source...
    22. 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. Diabetes Care 2004; 27(7): 1547-1553. Dostupné z DOI: <http://dx.doi.org/10.2337/diacare.27.7.1547>. Go to original source...
    23. Cummings SR, Black DM, Thompson DE et al. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. JAMA 1998; 280(24): 2077-2082. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.280.24.2077>. Go to original source...
    24. Dagdelen S, Sener D, and Bayraktar M. Influence of type 2 diabetes mellitus on bone mineral density response to bisphosphonates in late postmenopausal osteoporosis. Advances in Therapy 2007; 24(6): 1314-1320. Dostupné z DOI: <http://dx.doi.org/10.1007/BF02877778>. Go to original source...
    25. 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. Calcif Tissue Int 2016; 98(2): 114-122. Dostupné z DOI: <http://dx.doi.org/10.1007/s00223-015-0071-9>. Go to original source...
    26. Johnell O, Kanis JA, Black DM et al. Associations between Baseline Risk Factors and Vertebral Fracture Risk in the Multiple Outcomes of Raloxifene Evaluation (MORE) Study. J Bone Miner Res 2004; 19(5): 764-772. Dostupné z DOI: <http://dx.doi.org/10.1359/JBMR.040211> Go to original source...
    27. Hirano T. Pathophysiology of Diabetic Dyslipidemia. J Atheroscler Thromb 2018; 25(9): 771-782. Dostupné z DOI: <http://dx.doi.org/10.5551/jat.RV17023>. Go to original source...
    28. Jialal I, Singh G. Management of diabetic dyslipidemia: An update. World J Diabetes 2019; 10(5): 280-290. Dostupné z DOI: <http://dx.doi.org/10.4239/wjd.v10.i5.280>. Go to original source...
    29. Schwartz AV, Pavo I, Alam J et al. Teriparatide in patients with osteoporosis and type 2 diabetes. Bone 2016; 91 : 152-158. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bone.2016.06.017>. Go to original source...
    30. Langdahl BL, Silverman S, Fujiwara S et al. Real-world effectiveness of teriparatide on fracture reduction in patients with osteoporosis and comorbidities or risk factors for fractures: Integrated analysis of 4 prospective observational studies. Bone 2018; 116 : 58-66. Dostupné z DOI: <http://dx.doi.org/10.1016/j.bone.2018.07.013>. Go to original source...
    31. Cummings SR, San Martin J, McClung MR et al. Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis. N Engl J Med 2009; 361(8): 756-765. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa0809493>. Go to original source...
    32. Zebaze R, Libanati C, McClung MR et al. Denosumab Reduces Cortical Porosity of the Proximal Femoral Shaft in Postmenopausal Women With Osteoporosis. J Bone Miner Res 2016; 31(10): 1827-1834. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.2855>. Go to original source...
    33. Napoli N, Pannacciulli N, Vittinghoff E et al. Effect of denosumab on fasting glucose in women with diabetes or prediabetes from the FREEDOM trial. Diabetes Metab Res Rev 2018; 34(4): e2991. Dostupné z DOI: <http://dx.doi.org/10.1002/dmrr.2991>. Go to original source...
    34. Ferron M, Wei J, Yoshizawa T et al. Insulin signaling in osteoblasts integrates bone remodeling and energy metabolism. Cell 2010; 142(2): 296-308. Dostupné z DOI: <http://dx.doi.org/10.1016/j.cell.2010.06.003>. Go to original source...
    35. Schwartz AV, Schafer AL, Grey A et al. Effects of antiresorptive therapies on glucose metabolism: results from the FIT, HORIZON-PFT, and FREEDOM trials. J Bone Miner Res 2013; 28(6): 1348-1354. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.1865>. Go to original source...
    36. Karimi Fard M, Aminorroaya A, Kachuei et al. Alendronate improves fasting plasma glucose and insulin sensitivity, and decreases insulin resistance in prediabetic osteopenic postmenopausal women: A randomized triple-blind clinical trial. J Diabetes Investig 2019; 10(3): 731-737. Dostupné z DOI: <http://dx.doi.org/10.1111/jdi.12944>. Go to original source...
    37. Hayakawa N, Suzuki A. Diabetes mellitus and osteoporosis. Effect of antidiabetic medicine on osteoporotic fracture. Clin Calcium 2012; 22(9): 1383-1390.
    38. Jackuliak P, Kuzma M, PayerJ. Effect of antidiabetic treatment on bone. Physiol Res 2019; 68(Suppl 2): S107-S120. Dostupné z DOI: <http://dx.doi.org/10.33549/physiolres.934297>. Go to original source...
    39. Paul TV, Thomas N. Impact of oral antidiabetic agents on bone metabolism. Indian J Med Res 2015; 141(4): 385-388. Dostupné z DOI: <http://dx.doi.org/10.4103/0971-5916.159244>. Go to original source...
    40. McCarthy AD, Cortizo AM, Sedlinsky C. Metformin revisited: Does this regulator of AMP-activated protein kinase secondarily affect bone metabolism and prevent diabetic osteopathy. World J Diabetes 2016; 7(6): 122-133. Dostupné z DOI: <http://dx.doi.org/10.4239/wjd.v7.i6.122>. Go to original source...
    41. Gilbert MP, Pratley RE. The Impact of Diabetes and Diabetes Medications on Bone Health. Endocr Rev 2015; 36(2): 194-213. Dostupné z DOI: <http://dx.doi.org/10.1210/er.2012-1042>. Go to original source...
    42. Majumdar SR, Leslie WD, Lisa M Lix LM et al. Longer Duration of Diabetes Strongly Impacts Fracture Risk Assessment: The Manitoba BMD Cohort. J Clin Endocrinol Metab 2016; 101(11): 4489-4496. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2016-2569>. Go to original source...
    43. Yavropoulou M, Mousiolis A, Kolokouri V et al. Anti-diabetic treatment as an additional factor in a FRAX based evaluation of osteoporotic fracture risk. Endocrine Abstracts 2015; 37: EP300. Dostupné z DOI: <http://dx.doi.org/10.1530/endoabs.37.EP300>. Go to original source...
    44. Schwartz AV, Diabetes and Metabolism of Bone. In: Leahy J, Danoff A (eds). ENDO 2017: Meet-The-Professor Endocrine Case Management. Washington, DC 2017 : 63-65.
    45. Palermo A, D'Onofrio L, Eastell R et al. Oral anti-diabetic drugs and fracture risk, cut to the bone: safe or dangerous? A narrative review. Osteoporos Int 2015; 26(8): 2073-2089. Dostupné z DOI: <http://dx.doi.org/10.1007/s00198-015-3123-0>. Go to original source...
    46. Lecka-Czernik B. Safety of Anti-Diabetic Therapies on Bone. Clinical Rev Bone Miner Metab 2013; 11(1): 49-58. Dostupné z DOI: <http://dx.doi.org/10.1007/s12018-012-9129-7>. Go to original source...
    47. Molinuevo MS, Schurman L, McCarthy AD et al. Effect of metformin on bone marrow progenitor cell differentiation: In vivo and in vitro studies. J Bone Miner Res 2010; 25(2): 211-221. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.090732>. Go to original source...
    48. Sundararaghavan V, Mazur MM, Evans B et al. Diabetes and bone health: latest evidence and clinical implications. Ther Adv Musculoskelet Dis 2017; 9(3): 67-74. Dostupné z DOI: <http://dx.doi.org/10.1177/1759720X16687480>. Go to original source...
    49. Melton LJ, Leibson CL, Achenbach SJ et al. Fracture risk in type 2 diabetes: update of a population-based study. J Bone Miner Res 2008; 23(8): 1334-1342. Dostupné z DOI: <http://dx.doi.org/10.1359/jbmr.080323>. Go to original source...
    50. Russo GT, Giandalia A, Romeo EL et al. Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences. Int J Endocrinol 2016; 2016 : 1615735. <http://dx.doi.org/10.1155/2016/1615735>. Go to original source...
    51. Monami M, Cresci B, Colombini A et al. Bone fractures and hypoglycemic treatment in type 2 diabetic patients: a case-control study. Diabetes Care 2008; 31(2): 199-203. Dostupné z DOI: <http://dx.doi.org/10.2337/dc07-1736>. Go to original source...
    52. Lapane KL, Yang S, Brown MJ et al. Sulfonylureas and risk of falls and fractures: a systematic review. Drugs Aging 2013; 30(7): 527-547. Dostupné z DOI: <http://dx.doi.org/10.1007/s40266-013-0081-0>. Go to original source...
    53. Mehta S, Teigland C, Kfuri A et al. Comparative Safety of Oral Antidiabetic Therapy on Risk of Fracture in Patients with Diabetes. In American Diabetes Association 2014 Scientific Sessions 2014 : 165-OR.
    54. Tucker ME. Sulfonylureas May up Fracture Risk in Diabetes, along with TZDs. Medscape 2014. Dostupné z WWW: <https://www.medscape.com/viewarticle/826774>.
    55. Berberoglu Z, Yazici AC, Demirag NG. Effects of rosiglitazone on bone mineral density and remodelling parameters in Postmenopausal diabetic women: a 2-year follow-up study. Clin Endocrinol 2010; 73(3): 305-312. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1365-2265.2010.03784.x>. Go to original source...
    56. Mieczkowska A, Baslé MF, Chappard D et al. Thiazolidinediones induce osteocyte apoptosis by a G protein-coupled receptor 40-dependent mechanism. J Biol Chem 2012; 287(28): 23517-23526. Dostupné z DOI: <http://dx.doi.org/10.1074/jbc.M111.324814>. Go to original source...
    57. Loke YK, Singh S, Furberg CD. Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis. CMAJ 2009; 180(1): 32-39. Dostupné z DOI: <http://dx.doi.org/10.1503/cmaj.080486>. Go to original source...
    58. Fukunaga T, Zou W, Rohatgi N et al. An Insulin-Sensitizing Thiazolidinedione, Which Minimally Activates PPARγ, Does Not Cause Bone Loss. J Bone Miner Res 2015; 30(3): 481-488. Dostupné z DOI: <http://dx.doi.org/10.1002/jbmr.2364>. Go to original source...
    59. Ceccarelli E, Guarino EG, Merlotti D et al. Beyond Glycemic Control in Diabetes Mellitus: Effects of Incretin-Based Therapies on Bone Metabolism. Front Endocrinol (Lausanne) 2013; 4 : 73. Dostupné z DOI: <http://dx.doi.org/10.3389/fendo.2013.00073>. Go to original source...
    60. Monami M, Dicembrini I, Antenore A et al. Dipeptidyl peptidase-4 inhibitors and bone fractures: a meta-analysis of randomized clinical trials. Diabetes Care 2011; 34(11): 2474-2476. Dostupné z DOI: <http://dx.doi.org/10.2337/dc11-1099>. Go to original source...
    61. Nauck MA, Del Prato S, Meier JJ et al. Dapagliflozin versus Glipizide as Add-on Therapy in Patients with Type 2 Diabetes Who Have Inadequate Glycemic Control With Metformin: A randomized, 52-week, double-blind, active-controlled noninferiority trial. Diabetes Care 2011; 34(9): 2015-2022. Dostupné z DOI: <http://dx.doi.org/10.2337/dc11-0606>. Go to original source...
    62. List JF, Woo V, Enrique Morales E et al. Sodium-Glucose Cotransport Inhibition With Dapagliflozin in Type 2 Diabetes. Diabetes Care 2009; 32(4): 650-657. Dostupné z DOI: <http://dx.doi.org/10.2337/dc08-1863>. Go to original source...
    63. Ljunggren Ö, Bolinder J, Johansson L et al. Dapagliflozin has no effect on markers of bone formation and resorption or bone mineral density in patients with inadequately controlled type 2 diabetes mellitus on metformin. Diabetes Obes Metab 2012; 14(11): 990-999. Dostupné z DOI: <http://dx.doi.org/10.1111/j.1463-1326.2012.01630.x>. Go to original source...
    64. Kohan DE, Fioretto P, Tang W et al. Long-term study of patients with type 2 diabetes and moderate renal impairment shows that dapagliflozin reduces weight and blood pressure but does not improve glycemic control. Kidney Int 2014; 85(4): 962-971. Dostupné z DOI: <http://dx.doi.org/10.1038/ki.2013.356>. Go to original source...
    65. Watts NB, Bilezikian JP, Usiskin K et al. Effects of Canagliflozin on Fracture Risk in Patients With Type 2 Diabetes Mellitus. J Clin Endocrinol Metab 2016; 101(1): 157-166. Dostupné z DOI: <http://dx.doi.org/10.1210/jc.2015-3167>. Go to original source...
    66. Campos Pastor MM, López-Ibarra PJ, Escobar-Jiménez F et al. Intensive insulin therapy and bone mineral density in type 1 diabetes mellitus: a prospective study. Osteoporos Int 2000; 11(5): 455-459. Dostupné z DOI: <http://dx.doi.org/10.1007/s001980070114>. Go to original source...
    67. Fowlkes JL, Bunn RC, Thrailkill KM. Contributions of the Insulin/Insulin-Like Growth Factor-1 Axis to Diabetic Osteopathy. J Diabetes Metab 2011; 1(3): S1-003. Dostupné z DOI: <http://dx.doi.org/10.4172/2155-6156.S1-003>. Go to original source...
    68. Zhukouskaya VV, Shepelkevich AP, Chiodini I. Bone Health in Type 1 Diabetes: Where We Are Now and How We Should Proceed. Advances in Endocrinology 2014; 2014 : 12. Dostupné z DOI: <https://doi.org/10.1155/2014/982129>. Go to original source...
    69. Kanazawa I, Yamaguchi T, Yamamoto M et al. Relationships between serum adiponectin levels versus bone mineral density, bone metabolic markers, and vertebral fractures in type 2 diabetes mellitus. Eur J Endocrinol 2009? 160(2): 265-273. Dostupné z DOI: <http://dx.doi.org/10.1530/EJE-08-0642>. Go to original source...
    70. Chandran M. Diabetes Drug Effects on the Skeleton. Calcif Tissue Int 2017; 100(2): 133-149. Dostupné z DOI: <http://dx.doi.org/10.1007/s00223-016-0203-x>. Go to original source...
    71. Ferrari S. Diabetes and Bone. Calcif Tissue Int 2017; 100(2): 107-108. Dostupné z DOI: <http://dx.doi.org/10.1007/s00223-017-0234-y>. Go to original source...
    72. Quandt SA, Stafford JM, A Bell RA et al. Predictors of Falls in a Multiethnic Population of Older Rural Adults with Diabetes. J Gerontol A Biol Sci Med Sci 2006; 61(4): 394-398. Dostupné z DOI: <http://dx.doi.org/10.1093/gerona/61.4.394>. Go to original source...

    Return to the content


    Clinical Osteology

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.