Ponad 7000 publikacji medycznych!
Statystyki za 2021 rok:
odsłony: 8 805 378
Artykuły w Czytelni Medycznej o SARS-CoV-2/Covid-19

Poniżej zamieściliśmy fragment artykułu. Informacja nt. dostępu do pełnej treści artykułu
© Borgis - Postępy Nauk Medycznych 1/2017, s. 16-21
*Agata Bogołowska-Stieblich, Marek Tałałaj
Bone fractures in cancer patients
Złamania kości u pacjentów z chorobą nowotworową
Department of Geriatrics, Internal Medicine and Metabolic Bone Diseases, Centre of Postgraduate Medical Education, Warsaw
Head of Department: Associate Professor Marek Tałałaj, MD, PhD
Złamania kości w znaczący sposób zwiększają chorobowość i śmiertelność z powodu choroby podstawowej. U pacjentów z nowotworem istnieje wiele mechanizmów przyczyniających się do utraty masy kostnej. Mechanizmy te mogą być związane z chorobą podstawową oraz być następstwem terapii przeciwnowotworowej. Leczenie hormonalne stosowane u pacjentów z nowotworami hormonozależnymi może powodować hipogonadyzm i postępującą utratę masy kostnej. Chemioterapia stosowana u osób z chorobami nowotworowymi powoduje utratę masy kostnej, która nie ulega odbudowaniu po zakończeniu leczenia. Pacjenci z grupy podwyższonego ryzyka złamań osteoporotycznych powinni otrzymać właściwe leczenie tak szybko, jak to możliwe. Leczenie powinno zapewnić właściwą suplementację wapnia i witaminy D. Bisfosfoniany i denosumab są lekami z wyboru u pacjentów z chorobą nowotworową, gdyż są w stanie hamować utratę masy kostnej, redukować częstość złamań szkieletu i zmniejszać ryzyko wystąpienia hiperkalcemii i/lub hiperkalciurii.
Bone fractures significantly increase both morbidity and mortality of underlying diseases. Many mechanisms are responsible for bone loss among cancer patients, depending on underlying pathophysiological processes. The mechanisms can be related to the disease itself and the therapies used against cancer. Hormonal treatments used in patients with hormonally-responsive neoplasms can result in hypogonadism and progressive loss of bone mass. Chemotherapy employed in cancer patients causes a decrease in bone mass that is not recovered after discontinuation of the treatment. Patients at increased risk of fragility fractures should begin preventive treatment as soon as possible. The treatment need to assure adequate supplementation of calcium and vitamin D. Bisphosphonates and denosumab are the drugs of choice in patients with neoplastic diseases as they are able to inhibit bone mass loss, reduce the incidence of skeletal fractures and decrease the risk of hypercalcemia and/or hypercalciuria of malignancy.

Human skeleton is composed of two structural types of bone tissue: cortical bone, the dense outer layer of the skeleton responsible for supporting the weight of the body, and trabecular bone, the more metabolically active porous matrix located within short bones and ends of long bones. Bone tissue is undergoing continuous dynamic remodeling in a coupled and sequential process of bone resorption and formation, mediated by osteoclasts and osteoblasts respectively.
Many hormones and cytokines are involved in the close cross talk among cells within the bone microenvironment. Osteoclast proliferation and activity are stimulated by interleukin 6 (IL-6), IL-1, prostaglandins, and colony stimulating factors (CSFs) (1, 2). Activated osteoclasts bind to bone matrix via integrin proteins and secrete acid and lysosomal enzymes that degrade bone. Osteoblasts synthesize the collagenous precursors of bone matrix (osteoid) and regulate its mineralization. They are also involved in the control of osteoclast differentiation through expression of receptor activator of nuclear factor κB ligand (RANKL), and osteoprotegerin (OPG), a decoy RANK receptor, which inhibits osteoclast formation.
Cancer, after cardiovascular diseases, is the second leading cause of death (30% of total mortality). Its incidence and prevalence are still rising, partly due to aging of the population (2).
Multiple steps are involved in the development of metastases from a primary tumor to any distant site. These include angiogenesis, which provides nutritional support for tumor growth, local invasion through the basement membrane, adhesion to vessel endothelium in the target organs, and extravasation into the tissue. These events are supported by secretion of e.g. matrix metalloproteinases and cathepsin K by tumor cells (3, 4).
Bone remodeling units involve an overflow of growth factors, cell adhesion molecules, and cytokines that make them attractive sites for metastatic tumor cells. No definitive studies have linked increased bone resorption to increased tumor cell mass, but limiting of bone resorption was found to reduce tumor expansion in bone (5, 6).
Metastatic bone tumors consist of four types of radiographically defined lesions: osteolytic, osteoblastic, osteoporotic and mixed. Osteolytic lesions are characterized by the destruction of bone, recognized as a hole in the cortex on plain radiographic images. Osteoblastic lesions, often referred to as osteosclerotic, are characterized by excess deposition of new bone and appear on X-ray pictures as more dense bone. Osteoporotic lesions create areas of “faded” bone without cortical destruction and mixed lesions comprise a combination of bone destruction and new bone deposition. Mixed lesions often have a central clear area of cortical lysis surrounded by a zone of increased density (sclerosis). Osteolytic damages are most common in patients with breast cancer and multiple myeloma, while osteoblastic lesions in men with prostate cancer (7).
Bone metastases are usually located in the axial skeleton winded by valveless venous plexuses. The highly vascular metaphyseal tissue, composed predominantly of trabecular bone, appears to be the preferred site for bone metastases. The mechanics of its sluggish sinusoidal vascular supply give the invading tumor cells ample opportunity to move in and out of the marrow. The endothelial cells lining the sinusoids express multiple adhesion molecules, including P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1), and vascular cell adhesion molecule 1 (VCAM-1), that play key roles in extravasation of tumor cells into the marrow. Bone microenvironment contains many bone-stored cytokines and growth factors, such as insulin-like growth factor-1 (IGF-1), transforming growth factor beta (TGF-β), that appear to favor the growth of metastases (8).
In men the most common neoplasm is prostate cancer which develop osseous metastases in 90% of patients with generalized disease (9, 10). Bone metastases typically occur in the axial and/or proximal appendicular skeleton as osteosclerotic lesions, being the result of stimulation of osteoblasts by prostate cancer cells (7, 11).
Multiple myeloma (MM) is a hematological neoplasm characterized by the proliferation of cancerous plasma cells in the bone marrow and the presence of abnormal monoclonal protein in plasma and/or urine (12). Bone lesions are the result of imbalance between osteoclasts and osteoblasts activities. It was found that suppression of osteoblasts is caused mainly by inhibition of the Wingless/integrase-1 pathway, while an increase in the osteoclasts function is the result of amplification of the RANK/RANKL pathway and the activity of macrophage inflammatory protein 1-α (13, 14).
Bone scintigraphy is a nuclear scanning test that allows to diagnose a number of conditions relating to bones, including primary or metastatic neoplastic lesions, bone fractures not visible at traditional plain X-ray images, and damages to bones due to certain infections. The technique used for bone imaging utilizes labeling with Tc99mmethylene diphosphonate (Tc99mMDP) that is incorporated into bone tissue during its formation. It means that osteolytic lesions in patients with multiple myeloma are unlikely to be visualized. Metastatic cortical lesions may be best demonstrated on computed tomography, while trabecular lesions with magnetic resonance imaging. The lesions are found mostly at the bones with large quantity of bone marrow, such as cranium, spine, ribs, pelvis and proximal epiphyses of long bones. Increased bone resorption results in accelerated bone mass loss, hypercalcemia, and pathological fractures. Hypercalcemia is found in about 30-40% of patients, and pathological fractures are localized most often at the spine and may cause injury of the medulla (7, 14).
Various mechanisms responsible for bone loss in patients with neoplasm may exert different impact on the skeleton depending on the characteristics of the disease and therapies used against cancer. Some hormonal treatments employed in patients with breast or prostate cancers cause hypogonadism that accelerates bone mass loss. The chemotherapies, especially those including glucocorticoids, significantly decrease bone mineral density (BMD) and increase the risk of fractures (7, 11).
It has been documented that in women with localized breast cancer the incidence of vertebral fractures was almost five times greater than in healthy patients (odds ratio = 4.7), and in women with soft tissue metastases was over twenty times greater (OR = 22.7). Additional risk factors that increase bone fracture risk include treatment with aromatase inhibitors, low BMD (T-score < -1.5), elderly age > 65 years, low body mass index (< 20 kg/m2), personal history of fragility fracture after the age of 50 years, family history of hip fracture, systemic glucocorticoid use for more than 6 months, and cigarette smoking (15).
In men with advanced prostatic cancer treated with androgen deprivation therapy, who experienced at least one fracture after their diagnosis overall survival was significantly decreased compared with patients without fractures (median 121 vs 160 months) (16).
Treatments used in women with neoplastic diseases, such as surgical castration, hormonal treatment, radiation therapy and chemotherapy can result in hypogonadism and accelerated loss of bone tissue. Radiation therapy employed in advanced cancer of the uterine cervix and endometrium may contribute to the development of pelvic fractures. It was shown that focal, high dose radiation therapy can induce atrophy of the trabecular bone due to injury of blood vessels.

Powyżej zamieściliśmy fragment artykułu, do którego możesz uzyskać pełny dostęp.
Mam kod dostępu
  • Aby uzyskać płatny dostęp do pełnej treści powyższego artykułu albo wszystkich artykułów (w zależności od wybranej opcji), należy wprowadzić kod.
  • Wprowadzając kod, akceptują Państwo treść Regulaminu oraz potwierdzają zapoznanie się z nim.
  • Aby kupić kod proszę skorzystać z jednej z poniższych opcji.

Opcja #1


  • dostęp do tego artykułu
  • dostęp na 7 dni

uzyskany kod musi być wprowadzony na stronie artykułu, do którego został wykupiony

Opcja #2


  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 30 dni
  • najpopularniejsza opcja

Opcja #3


  • dostęp do tego i pozostałych ponad 7000 artykułów
  • dostęp na 90 dni
  • oszczędzasz 28 zł
1. Rubens RD: Bone metastases: incidence and complications. [In:] Rubens RD, Mundy GR (eds.): Cancer and the Skeleton. Martin Dunitz, London 2000: 33-42.
2. Rosen LS, Gordon D, Tchekmedyian S et al.: Zoledronic acid versus placebo in the treatment of skeletal metastases in patients with lung cancer and other solid tumors: a phase III, double-blind, randomized trial. J Clin Oncol 2003; 21: 3150-3157.
3. Bussard KM, Gay CV, Mastro AM: The bone microenvironment in metastasis; what is special about bone? Cancer Metastasis Rev 2008; 27: 41-55.
4. Chambers AF, Groom AC, MacDonald IC: Dissemination and growth of cancer cells in metastatic sites. Nat Rev Cancer 2002; 2: 563-572.
5. Sasaki A, Boyce BF, Story B et al.: Bisphosphonate risedronate reduces metastatic human breast cancer burden in bone in nude mice. Cancer Res 1995; 55: 3551-3557.
6. Powles T, Paterson S, Kanis JA et al.: Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer. J Clin Oncol 2002; 20: 3219-3224.
7. Coleman RE: Clinical features of metastatic bone disease and risk of skeletal morbidity. Clin Cancer Res 2006; 12: 6243s-6249s.
8. Yoneda T, Hiraga T: Crosstalk between cancer cells and bone microenvironment in bone metastasis. Biochem Biophys Res Commun 2005; 328: 679-687.
9. Siegel RL, Miller KD, Jemal A: Cancer statistics 2015. CA Cancer J Clin 2015; 65: 5-29.
10. Bubendorf L, Schopfer A, Wagner U et al.: Metastatic patterns of prostate cancer: an autopsy study of 1,589 patients. Hum Pathol 2000; 31: 578-583.
11. Mundy GR: Metastasis to bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2002; 2: 584-593.
12. Palumbo A, Anderson K: Multiple myeloma. N Engl J Med 2011; 364: 1046-1060.
13. Tricot G: Multiple myeloma and other plasma cell disorders. [In:] Hoffmann R: Hematology, Basic Principle and Practice. 4th ed. Churchil-Livingstone/Elsevier, London 2005: 1501-1535.
14. Terpos E, Dimopoulos MA: Myeloma bone disease: pathophysiology and management. Ann Oncol 2005; 16: 1223-1231.
15. Kanis JA, McCloskey EV, Powles T: A high incidence of vertebral fracture in women with breast cancer. Br J Cancer 1999; 79: 1179-1181.
16. Oefelein MG, Ricchiuti V, Conrad W et al.: Skeletal fractures negatively correlate with overall survival in men with prostate cancer. J Urol 2002; 168: 1005-1007.
17. Hung YC, Yeh LS, Chang WC et al.: Prospective study of decreased bone mineral density in patients with cervical cancer without bone metastases: A preliminary report. Jpn J Clin Oncol 2002; 32: 422-424.
18. Ottanelli S: Prevention and treatment of bone fragility in cancer patient. Clin Cases Miner Bone Metab 2015; 2: 116-129.
19. An K-C: Selective estrogen receptor modulators. Asian Spine J 2016; 10: 787-791.
20. Hadji P: Aromatase inhibitor-associated bone loss in breast cancer patients is distinct from postmenopausal osteoporosis. Crit Rev Oncol Hematol 2009; 69: 73-82.
21. Coleman RE, Banks LM, Girgis SI et al.: Skeletal effects of exemestane on bone mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncol 2007; 8: 119-127.
22. Forbes JF, Cuzick J, Buzdar A et al.: Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008; 9: 45-53.
23. Rabaglio M, Sun Z, Price KN et al.: Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial. Ann Oncol 2009; 20: 1489-1498.
24. Coombes RC, Kilburn LS, Snowdon CF et al.: Survival and safety of exemestane versus tamoxifen after 2-3 years’ tamoxifen treatment (Intergroup Exemestane Study): a randomised controlled trial. Lancet 2007; 369: 559-570.
25. Goss PE, Ingle JN, Martino S et al.: Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor positive breast cancer: updated findings from NCIC CTG MA.17. J Natl Cancer Inst 2005; 97: 1262-1271.
26. Diamond T, Campbell J, Bryant C et al.: The effect of combined androgen blockade on bone turnover and bone mineral densities in men treated for prostate carcinoma: longitudinal evaluation and response to intermittent cyclic etidronate therapy. Cancer 1998; 83: 1561-1566.
27. Chernichenko OA, Sakalo VS, Yakovlev PG et al.: Effect of androgen suppression on bone mineral density in patients with prostate cancer. Exp Oncol 2014; 36: 276-278.
28. Lassemillante AC, Doi SA, Hooper JD et al.: Prevalence of osteoporosis in prostate cancer survivors II: a meta-analysis of men not on androgen deprivation therapy. Endocrine 2015; 50: 344-354.
29. Garcıa-Sanz R, Alegre A, Capote FJ et al.: Guidelines for the use of bisphosphonates in multiple myeloma: recommendations of the expert committee of the Spanish Myeloma Group from the PETHEMA group. Med Clin (Barc) 2010; 134: 268-278.
30. Roelofs AJ, Thompson K, Ebetino FH et al.: Bisphosphonates: molecular mechanisms of action and effects on bone cells, monocytes and macrophages. Curr Pharm Des 2010; 16: 2950-2960.
31. Coleman R, Gnant M, Morgan G, Clezardin P: Effects of bone-targeted agents on cancer progression and mortality. J Natl Cancer Inst 2012; 104: 1059-1067.
32. Wong R, Wiffen PJ: Bisphosphonates for the relief of pain secondary to bone metastases. Cochrane Database Syst Rev 2002; 2: CD002068
33. Tolia M, Zygogianni A, Kouvaris JR et al.: Bisphosphonates in the treatment of cancer patients. Anticancer Res 2014; 34: 23-38.
34. Stachnika A, Yuena T, Iqbala J et al.: Repurposing of bisphosphonates for the prevention and therapy of non small cell lung and breast cancer. PNAS 2014; 111: 17995-18000.
35. Yuen T, Stachnik A, Iqbal J et al.: Bisphosphonates inactivate human EGFRs to exert antitumor actions. Proc Natl Acad Sci USA 2014; 111: 17989-17994.
36. Coleman R, de Boer R, Eidtmann H et al.: Zoledronic acid (zoledronate) for postmenopausal women with early breast cancer receiving adjuvant letrozole (ZO-FAST study): Final 60-month results. Ann Oncol 2013; 24: 398-405.
37. Gnant M, Mlineritsch B, Schippinger W et al.: Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 2009; 360: 679-691.
38. Pazianas M, Abrahamsen B, Eiken PA et al.: Reduced colon cancer incidence and mortality in postmenopausal women treated with an oral bisphosphonate – Danish National Register Based Cohort Study. Osteoporos Int 2012; 23: 2693-2701.
39. Aksoy S, Sendur MAN, Altundag K: Demographic and clinico-pathological characteristics of breast cancer patients with history of oral alendronate use. Med Oncol 2012; 29: 2601-2605.
40. Terpos E, Morgan G, Dimopoulos MA et al.: International Myeloma Working Group recommendations for the treatment of multiple myeloma-related bone disease. J Clin Oncol 2013; 31: 2347-2357.
41. Brown JE, Coleman RE: Denosumab in patients with cancer-a surgical strike against the osteoclast. Nat Rev Clin Oncol 2012; 9: 110-118.
42. Body JJ, Facon T, Coleman RE et al.: A study of the biological receptor activator of nuclear factor-κB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 2006; 12: 1221-1228.
43. Fizazi K, Lipton A, Mariette X et al.: Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 2009; 27: 1564-1571.
44. Reid IR, Miller P, Lyles K et al.: Comparison of a single infusion of zoledronic acid with risedronate for Paget’s disease. N Engl J Med 2005; 353: 898-908.
45. Wang Z, Qiao D, Lu Y et al.: Systematic literature review and network meta-analysis comparing bone-targeted agents for the prevention of skeletal-related events in cancer patients with bone metastasis. Oncologist 2015; 20: 440-449.
46. Hoff AO, Toth B, Altundag K et al.: Osteonecrosis of the jaw in patients receiving intravenous bisphosphonate therapy. J Bone Min Res 2005; 20: S55.
47. Płudowski P, Karczmarewicz E, Bayer M et al.: Practical guidelines for the supplementation of vitamin D and the treatment of deficits in Central Europe-recommended vitamin D intakes in the general population and groups at risk of vitamin D deficiency. Endokrynol Pol 2013; 64: 319-327.
48. International Osteoporosis Foundation: Osteoporosis and You; http:// www.iofbonehealth.org/download/osteofound/filemanager/publications/pdf/osteoporosis_and_you.pdf (2.08.2010).
otrzymano: 2016-12-07
zaakceptowano do druku: 2016-12-28

Adres do korespondencji:
*Agata Bogołowska-Stieblich
Department of Geriatrics, Internal Medicine and Metabolic Bone Diseases Centre of Postgraduate Medical Education
Czerniakowska 231, 00-416 Warszawa
tel. +48 (22) 584-11-47

Postępy Nauk Medycznych 1/2017
Strona internetowa czasopisma Postępy Nauk Medycznych