Verlaufsdiagnostik des Knochenstoffwechsels unter verschiedenen Therapieformen

 

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Zusammenfassung

Osteoporose ist per se eine chronische Erkrankung, daher sind neben nichtpharmakologischen Interventionen (z. B. hinsichtlich Ernährung und Bewegung) vor allem medikamentöse Behandlungen durch Antiresorptiva, osteoanabole oder dual wirksame Medikamente im individuellen Kontext für viele Jahre zu planen. Für ein Langzeit-Monitoring dieser Therapien kommen bildgebende Verfahren wie die Knochendichtemessung, Risiko-Algorithmen, aber auch die Messung von Knochenstoffwechselmarkern in Betracht. Während Knochendichtemessungen aufgrund der nur langsamen Umstellung der Knochenstruktur und -dichte in mehrjährigen Abständen sinnvoll sind, ermöglichen Labormessungen als Surrogatmarker eine Momentaufnahme des individuellen Knochenumsatzes und die Beurteilung der Medikamentenwirkung oder eines Risikos bei Therapiepause in wesentlich kürzeren Abständen und mit wenig Aufwand. Im Folgenden werden Labormarker des Knochenstoffwechsels in Hinblick auf Langzeittherapie, Kombinations- oder Sequenztherapie und das Management von Therapiepausen hin beleuchtet, um individuelle Behandlungsstrategien für Osteoporose-Betroffene planen und kontrollieren zu können. Dabei wird auch auf spezielle Personengruppen bzw. sekundäre Formen von Osteoporose eingegangen und auf neue Entwicklungen für die Zukunft des Osteoporose-Monitorings hingewiesen.

Abstract

Osteoporosis is per se a chronic disease, requiring non-pharmacological interventions such as nutritional and training adaptations, but also a long-term use of bone-specific pharmacological treatments, including antiresorptive and/or osteoanabolic or even dual approaches. Imaging options such as bone density measurements, risk algorithms and the assessment of bone turnover are necessary for the monitoring of such therapies. While bone density measurements during monitoring of treatment are only useful in more than annual intervals due to the slow reaction of bone structure and density to therapeutic interventions, lab-based analyses of bone turnover are surrogate markers for individual “flash-lights” of bone metabolism and easy-to-access information in shorter intervals of choice. This review aims to discuss markers of bone metabolism in view of long-term strategies, combination and sequential therapy and the management of drug holidays as a tool to monitor individual reactions and needs of pharmacological therapy options. Specific patient groups or secondary forms of osteoporosis will be discussed as well as new developments for the future monitoring of patients with osteoporosis.

Publication History

Received: 14 June 2023

Accepted: 13 September 2023

Article published online:
05 October 2023

© 2023. Thieme. All rights reserved.

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• Literatur

• 1 Schmidmaier, Ralf; Hadji, Peyman; Kern, Peter; Drey, Michael; Jakob, Franz; Thomasius, Friederike – Recommendations for the Pharmacological Treatment of Osteoporosis – Update 2023 of the German Osteoporosis Guideline, Osteologie 2023; 32(02): 115–122
• 2 Carey JJ, Chih-Hsing Wu P, Bergin D. Risk assessment tools for osteoporosis and fractures in 2022. Best Pract Res Clin Rheumatol 2022; 36 DOI: 10.1055/a-2053-7047.
  Article in Thieme ConnectGoogle Scholar
• 3 Glüer, Claus-C.; Engelke, Klaus; Thomasius, Friederike – Das Konzept des DVO Frakturrisikorechners, Osteologie 2023; 32(02): 123 – 132
• 4 Vlot MC. et al. Clinical utility of bone markers in various diseases. Bone 2018; vol. 114: 215-225
  CrossrefPubMedGoogle Scholar
• 5 Bjarnason NH, Henriksen EE, Alexandersen P, Christgau S, Henriksen DB, Christiansen C. Mechanism of circadian variation in bone resorption. Bone 2002; 30: 307-313
  CrossrefPubMedGoogle Scholar
• 6 Naylor KE. et al. Response of bone turnover markers to three oral bisphosphonate therapies in postmenopausal osteoporosis: the TRIO study. Osteoporos. Int. 2016; 27: 21-31
  CrossrefPubMedGoogle Scholar
• 7 Eastell R. et al. Bone turnover markers: Are they clinically useful? . Eur J Endocrinol 2018; 178: R19-R31
  CrossrefPubMedGoogle Scholar
• 8 Bieglmayer C, Dimai HP, Gasser RW, Kudlacek S, Obermayer-Pietsch B, Woloszczuk W, Zwettler E, Griesmacher A. Biomarkers of bone turnover in diagnosis and therapy of osteoporosis: a consensus advice from an Austrian working group. Wien Med Wochenschr 2012; 162: 464-477
  CrossrefPubMedGoogle Scholar
• 9 Foundation for the National Institutes of Health (FNIH) Bone Quality Project. Eastell R, Black DM, Lui LY, Chines A, Marin F, Khosla S, de Papp AE, Cauley JA, Mitlak B, McCulloch CE, Vittinghoff E, Bauer DC. Treatment-Related Changes in Bone Turnover and Fracture Risk Reduction in Clinical Trials of Antiresorptive Drugs: Proportion of Treatment Effect Explained. J Bone Miner Res 2021; 36: 236-243
  CrossrefPubMedGoogle Scholar
• 10 EUROFORS Study Group. Blumsohn A, Marin F, Nickelsen T, Brixen K, Sigurdsson G, González de la Vera J, Boonen S, Liu-Léage S, Barker C, Eastell R. Early changes in biochemical markers of bone turnover and their relationship with bone mineral density changes after 24 months of treatment with teriparatide. Osteoporos Int 2011; 22: 1935-1946
  CrossrefPubMedGoogle Scholar
• 11 EUROFORS Investigators. Boonen S, Marin F, Obermayer-Pietsch B, Simões ME, Barker C, Glass EV, Hadji P, Lyritis G, Oertel H, Nickelsen T, McCloskey EV. Effects of previous antiresorptive therapy on the bone mineral density response to two years of teriparatide treatment in postmenopausal women with osteoporosis. J Clin Endocrinol Metab 2008; 93: 852-860 DOI: 10.1210/jc.2007-0711.
  CrossrefPubMedGoogle Scholar
• 12 McClung MR, Grauer A, Boonen S, Bolognese MA, Brown JP, Diez-Perez A, Langdahl BL, Reginster JY, Zanchetta JR, Wasserman SM, Katz L, Maddox J, Yang YC, Libanati C, Bone HG. Romosozumab in postmenopausal women with low bone mineral density. N Engl J Med 2014; 370: 412-420
  CrossrefPubMedGoogle Scholar
• 13 Langdahl B. Treatment of postmenopausal osteoporosis with bone-forming and antiresorptive treatments: Combined and sequential approaches. Bone 2020; 139: 115516
  CrossrefPubMedGoogle Scholar
• 14 Kendler DL, Roux C, Benhamou CL, Brown JP, Lillestol M, Siddhanti S, Man HS, San Martin J, Bone HG. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 2010; 25: 72-81
  CrossrefPubMedGoogle Scholar
• 15 Geusens P, Marin F, Kendler DL, Russo LA, Zerbini CA, Minisola S, Body JJ, Lespessailles E, Greenspan SL, Bagur A, Stepan JJ, Lakatos P, Casado E, Moericke R, López-Romero P, Fahrleitner-Pammer A. Effects of Teriparatide Compared with Risedronate on the Risk of Fractures in Subgroups of Postmenopausal Women with Severe Osteoporosis: The VERO Trial. J Bone Miner Res 2018; 33: 783-794
  CrossrefPubMedGoogle Scholar
• 16 Leder BZ, Tsai JN, Uihlein AV, Wallace PM, Lee H, Neer RM, Burnett-Bowie SA. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet 2015; 386: 1147-1155
  CrossrefPubMedGoogle Scholar
• 17 Takada J, Dinavahi R, Miyauchi A, Hamaya E, Hirama T, Libanati C, Nakamura Y, Milmont CE, Grauer A. Relationship between P1NP, a biochemical marker of bone turnover, and bone mineral density in patients transitioned from alendronate to romosozumab or teriparatide: a post hoc analysis of the STRUCTURE trial. J Bone Miner Metab 2020; 38: 310-315
  CrossrefPubMedGoogle Scholar
• 18 Muschitz C, Kocijan R, Fahrleitner-Pammer A, Pavo I, Haschka J, Schima W, Kapiotis S, Resch H. Overlapping and continued alendronate or raloxifene administration in patients on teriparatide: effects on areal and volumetric bone mineral density – the CONFORS Study. J Bone Miner Res 2014; 29: 1777-1785 DOI: 10.1002/jbmr.2216.
  CrossrefPubMedGoogle Scholar
• 19 Cosman F, Wermers RA, Recknor C, Mauck KF, Xie L, Glass EV, Krege JH. Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent. J Clin Endocrinol Metab 2009; 94: 3772-3780
  CrossrefPubMedGoogle Scholar
• 20 Tsourdi E, Langdahl B, Cohen-Solal M, Aubry-Rozier B, Eriksen EF, Guañabens N, Obermayer-Pietsch B, Ralston SH, Eastell R, Zillikens MC. Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS. Bone. 2017; 105: 11-17
  CrossrefPubMedGoogle Scholar
• 21 Wang M, Wu YF, Girgis CM. Bisphosphonate Drug Holidays: Evidence From Clinical Trials and Real-World Studies. JBMR Plus 2022; vol. 6: e10629
  CrossrefPubMedGoogle Scholar
• 22 Lewiecki EM. Evaluating Patients for Secondary Causes of Osteoporosis. Curr. Osteoporos. Rep. 2022; 20: 1-12
  CrossrefPubMedGoogle Scholar
• 23 Salam S, Gallagher O, Gossiel F, Paggiosi M, Khwaja A, Eastell R. Diagnostic Accuracy of Biomarkers and Imaging for Bone Turnover in Renal Osteodystrophy. J Am Soc Nephrol 2018; 29: 1557-1565
  CrossrefPubMedGoogle Scholar
• 24 Diabetes Working Group. Napoli N, Chandran M, Pierroz DD, Abrahamsen B, Schwartz AV, Ferrari SL, Bone IOF. Mechanisms of diabetes mellitus-induced bone fragility. Nat Rev Endocrinol 2017; 13: 208-219
  CrossrefPubMedGoogle Scholar
• 25 Lademann F, Tsourdi E, Hofbauer LC, Rauner M. Thyroid Hormone Actions and Bone Remodeling – The Role of the Wnt Signaling Pathway. Exp Clin Endocrinol Diabetes 2020; 128: 450-454
  Article in Thieme ConnectPubMedGoogle Scholar
• 26 Torregrosa JV, Ferreira AC, Cucchiari D, Ferreira A. Bone Mineral Disease After Kidney Transplantation. Calcif Tissue Int 2021; 108: 551-560
  CrossrefPubMedGoogle Scholar
• 27 Compston J. Glucocorticoid-induced osteoporosis: an update. Endocrine 2018; 61: 7-16
  CrossrefPubMedGoogle Scholar
• 28 Hussain MS, Mazumder T. Long-term use of proton pump inhibitors adversely affects minerals and vitamin metabolism, bone turnover, bone mass, and bone strength. J Basic Clin Physiol Pharmacol 2021; 33: 567-579
  CrossrefPubMedGoogle Scholar
• 29 Song MK, Park SI, Cho SW. Circulating biomarkers for diagnosis and therapeutic monitoring in bone metastasis. J Bone Miner Metab 2023; 41: 337-344
  CrossrefPubMedGoogle Scholar
• 30 Dincel AS, Jørgensen NR. IOF-IFCC Joint Committee on Bone Metabolism (C-BM). New Emerging Biomarkers for Bone Disease: Sclerostin and Dickkopf-1 (DKK1). Calcif Tissue Int 2023; 112: 243-257
  CrossrefPubMedGoogle Scholar
• 31 Nguyen HH, van de Laarschot DM, Verkerk AJMH, Milat F, Zillikens MC, Ebeling PR. Genetic Risk Factors for Atypical Femoral Fractures (AFFs): A Systematic Review. JBMR Plus 2018; 2: 1-11
  CrossrefPubMedGoogle Scholar
• 32 Foessl I, Bassett JHD, Bjørnerem Å, Busse B, Calado Â, Chavassieux P, Christou M, Douni E, Fiedler IAK, Fonseca JE, Hassler E, Högler W, Kague E, Karasik D, Khashayar P, Langdahl BL, Leitch VD, Lopes P, Markozannes G, McGuigan FEA, Medina-Gomez C, Ntzani E, Oei L, Ohlsson C, Szulc P, Tobias JH, Trajanoska K, Tuzun Ş, Valjevac A, van Rietbergen B, Williams GR, Zekic T, Rivadeneira F, Obermayer-Pietsch B. Bone Phenotyping Approaches in Human, Mice and Zebrafish – Expert Overview of the EU Cost Action GEMSTONE (“GEnomics of MusculoSkeletal traits TranslatiOnal NEtwork”). Front Endocrinol (Lausanne) 2021; 12: 720728 DOI: 10.3389/fendo.2021.720728.
  CrossrefPubMedGoogle Scholar
• 33 Nevola KT, Kiel DP, Zullo AR, Weiss S, Homuth G, Foessl I, Obermayer-Pietsch B, Motyl KJ, Lary CW. miRNA Mechanisms Underlying the Association of Beta Blocker Use and Bone Mineral Density. J Bone Miner Res 2021; 36: 110-122 DOI: 10.1002/jbmr.4160.. Epub 2020 Sep 22
  CrossrefPubMedGoogle Scholar
• 34 Qin Y, Wang L, Gao Z, Chen G, Zhang C. Bone marrow stromal/stem cell-derived extracellular vesicles regulate osteoblast activity and differentiation in vitro and promote bone regeneration in vivo. Sci. Reports 2016; 61: 1-11
  Google Scholar