Eight pillars of oncorheumatology: Crossroads between malignancies and musculoskeletal diseases.

ONCORHEUMATOLOGY: RELATIONSHIP BETWEEN MALIGNANCIES AND MUSCULOSKELETAL DISEASES: Oncorheumatology is the meeting point of tumor formation and rheumatic musculoskeletal diseases (RMD). Multiple interactions exist between these two medical specialties. One major field is the topic of malignancies associated with rheumatic diseases, while the other topic covers the development of musculoskeletal disease in cancer patients. Within the first group, secondary malignancies may be associated with rheumatic diseases. Mostly sustained inflammation is responsible for transition into cancer. Tumor-associated antigens (TAA) with adhesive properties are present on tumor cells. These molecules may also be expressed by inflammatory leukocytes and soluble TAA levels may be elevated in RMDs. There has been continuous debate with respect to the possible carcinogenicity of conventional and targeted antirheumatic drugs. Very recent data from registries suggest that neither biologics, nor JAK inhibitors increase cancer risk in arthritis patients. The issue of physiotherapy in rheumatic patients with recent or current cancer has also been controversial. Some modalities, primarily exercise, may be safely applied to patients with RMD and cancer. The second large topic includes paraneoplastic syndromes. Musculoskeletal paraneoplasias are triggered by tumor-derived mediators. These syndromes are sometimes slightly different from the classical RMDs. Various chemotherapies may also be associated with autoimmune side effects. Recently, these immune-related complications have also been observed in cancer patients treated with immune-checkpoint inhibitors. Sex hormone-deprivation therapies, such as aromatase inhibitors and anti-androgens are widely used for the treatment of breast and prostate cancer, respectively. These compounds may induce bone loss and lead to osteoporosis. Finally, primary and secondary malignancies of the musculoskeletal system may also interest rheumatologists. In this review, the clinical, practical aspects of these eight pillars of oncorheumatology will be discussed.

Oncorheumatology: relationship between malignancies and musculoskeletal diseases / Onkoreumatológia: a daganatos és mozgásszervi kórképek összefüggései

Oncorheumatology is the meeting point of tumour formation and rheumatic diseases. Multiple interactions exist between these two medical specialties. One major field is the topic of malignancies associated with rheumatic diseases, while the other topic covers the development of musculoskeletal disease in cancer patients. In the first group, secondary malignancies associated with rheumatic diseases, role of tumour-associated antigens in rheumatology, the possible carcinogenicity of conventional and targeted antirheumatic drugs and physical therapy of rheumatic patients with recent or current cancer will be discussed. The second large topic includes paraneoplastic syndromes, autoimmune-rheumatic side effects of oncotherapies (chemotherapy and immunotherapy), effects of hormone-deprivation therapies on bone and primary and secondary malignancies of the musculoskeletal system. Orv Hetil. 2020; 161(28): 1151-1165.

Laser-induced plasma spectroscopy (LIPS): use of a geological tool in assessing bone mineral content.

Bone may be similar to geological formulations in many ways. Therefore, it may be logical to apply laser-based geological techniques in bone research. The mineral and element oxide composition of bioapatite can be estimated by mathematical models. Laser-induced plasma spectrometry (LIPS) has long been used in geology. This method may provide a possibility to determine the composition and concentration of element oxides forming the inorganic part of bones. In this study, we wished to standardize the LIPS technique and use mathematical calculations and models in order to determine CaO distribution and bone homogeneity using bovine shin bone samples. We used polished slices of five bovine shin bones. A portable LIPS instrument using high-power Nd++YAG laser pulses has been developed (OpLab, Budapest). Analysis of CaO distribution was carried out in a 10 × 10 sampling matrix applying 300-µm sampling intervals. We assessed both cortical and trabecular bone areas. Regions of interest (ROI) were determined under microscope. CaO peaks were identified in the 200-500 nm wavelength range. A mathematical formula was used to calculate the element oxide composition (wt%) of inorganic bone. We also applied two accepted mathematical approaches, the Bartlett's test and frequency distribution curve-based analysis, to determine the homogeneity of CaO distribution in bones. We were able to standardize the LIPS technique for bone research. CaO concentrations in the cortical and trabecular regions of B1-5 bones were 33.11 ± 3.99% (range 24.02-40.43%) and 27.60 ± 7.44% (range 3.58-39.51%), respectively. CaO concentrations highly corresponded to those routinely determined by ICP-OES. We were able to graphically demonstrate CaO distribution in both 2D and 3D. We also determined possible interrelations between laser-induced craters and bone structure units, which may reflect the bone structure and may influence the heterogeneity of CaO distributions. By using two different statistical methods, we could confirm if bone samples were homogeneous or not with respect to CaO concentration distribution. LIPS, a technique previously used in geology, may be included in bone research. Assessment of element oxide concentrations in the inorganic part of bone, as well as mathematical calculations may be useful to determine the content of CaO and other element oxides in bone, further analyze bone structure and homogeneity and possibly apply this research to normal, as well as diseased bones.

[Physiotherapy of cancer patients]. / Daganatos betegek fizioterápiája.

Physiotherapy of cancer patients is one of the most controversial issues in our country. Malignant diseases are firstly mentioned as a contraindication of physiotherapy. Until now, physiotherapy was not suggested (or only in limited accessibility) for those patients who had malignant disease in medical history. International medical practice was less restrictive in managing this topic. The development of imaging techniques put this question in a new light. On the basis of evidence, the majority of articles have reported beneficial effects of physiotherapy in cancer patients, and only few articles mentioned it as harmful. Of course, each patient requires an individual assessment, however, if we exclude the possibility of tumor recurrence and metastasis, most of physiotherapy procedures can be used safely. One of the aims of this review is to support the physicians' decisions when to prescribe treatments, in such a way, that more patients could receive physiotherapy. Orv. Hetil., 2016, 157(31), 1224-1231.

In vivo calcium and phosphate iontophoresis for the topical treatment of osteoporosis.

BACKGROUND: In addition to systemic treatment, osteoporosis may be treated topically by incorporating calcium and phosphate into the bone. OBJECTIVE: This article describes the use of a recently developed, novel iontophoretic apparatus suitable for local ion delivery into bones. In this study, in vivo experiments were performed to compare the effects of local electrotherapy and those of systemic hormone replacement on bone. DESIGN: In this study, local iontophoresis was carried out in ovariectomized and control rats. Bone density, biomechanical, and elemental studies were performed. METHODS: Forty 12-week-old Sprague-Dawley rats received an ovariectomy (OVX) or were sham-operated (sham). Twenty-one weeks later, tibias of subgroups of sham-operated and OVX animals were subjected to serial local iontophoresis (IOP) treatments, received systemic subcutaneous 17ß-estradiol (E2), or were treated with the combination of IOP and E2. Changes in bone density were detected by quantitative ultrasound densitometry and expressed as amplitude-dependent speed of sound (AD-SoS). Biomechanical studies and elemental analysis were performed at the end of the experiments. RESULTS: Osteopenia developed 21 weeks after OVX in the proximal tibial regions; the mean difference estimate (95% confidence intervals) of AD-SoS values between the sham-operated and OVX animals was 188.7 (140.4-237.1). Serial iontophoretic treatment resulted in an increase in bone density in both sham-operated and OVX animals (sham+IOP versus sham: 121.4 [73.01-169.7]; OVX+IOP versus OVX: 241.6 [193.2-289.9]). Similar changes in AD-SoS were detected after 17ß-estradiol (E2) treatment; however, even greater changes occurred after OVX+E2+IOP versus OVX+E2 (123.4 [75.1-171.8]). Similar improvements also were evident regarding the biomechanical features of the tibias. LIMITATIONS: A limitation of this study was the relatively small number of rats. CONCLUSIONS: The efficacy of local IOP using calcium- and phosphate-donating microparticles is comparable to that of estrogen therapy as evidenced by steadily increasing bone density, restoration of the calcium and phosphate balance, and improvement in the biomechanical properties of the bone.

Periosteal microcirculatory action of chronic estrogen supplementation in osteoporotic rats challenged with tourniquet ischemia.

AIMS: Transient ischemia of osteoporotic bones during elective orthopedic surgery or fracture repair carries risks for serious complications, and estrogen loss or replacement has a potential to influence ischemia-reperfusion-induced inflammatory activation. To clarify this, we investigated the periosteal inflammatory changes in a clinically relevant time frame in ovariectomized rats, an experimental model of postmenopausal bone loss. Furthermore, the effects of chronic estrogen supplementation on the postischemic local and systemic inflammatory reactions were assessed. MAIN METHODS: Bilateral ovariectomy or sham operation was performed in 3-month-old female Sprague-Dawley rats. Five months later, estrogen replacement therapy with 17ß-estradiol (20 µg(-1) kg(-1) day(-1)) or vehicle treatment was initiated. The microcirculatory inflammatory consequences of 60-min total hindlimb ischemia followed by 180-min reperfusion were examined 11 months after ovariectomy and were compared with those in 3-month-old animals. KEY FINDINGS: The osteoporosis that developed 5 months after ovariectomy was significantly ameliorated by estrogen replacement therapy. Both in ovariectomized and in non-ovariectomized animals, ischemia-reperfusion elevated the neutrophil adherence ~3-fold in the postcapillary venules of the periosteum (intravital microscopy), with an ~50-60% increase in intravascular neutrophil activation (CD11b; FACS analysis), an enhanced TNF-α release (ELISA) and periosteal expression of ICAM-1 (the endothelial ligand of CD11b; immunohistochemistry). Exogenous 17ß-estradiol considerably reduced TNF-α release and the number of neutrophil-endothelial interactions in the periosteum, without affecting the CD11b and ICAM-1 expression changes. SIGNIFICANCE: Osteoporosis itself does not increase the magnitude of the limb ischemia-reperfusion-associated periosteal inflammatory reaction. Chronic estrogen supplementation, however, reverses osteoporosis and significantly ameliorates the microcirculatory consequences of transient ischemia.

Development of natural calcium- and phosphate-donating microparticles and a new iontophoretic apparatus for the topical treatment of local osteoporosis. Preliminary in vitro and in vivo studies.

AIM: We wished to develop a new iontophoretic device suitable for the treatment of local bone loss such as after fractures or in osteodystrophy. METHODS: The new iontophoretic apparatus consists of two parts. The first part consists of two natural-based, chemically modified particles as potential medicines, while the other part is a 3-electrode electrophoretic device based on a new principle. This device 'knocks out' Ca²(+) and PO4 ³â» ions from the particles with its impulse-like positive and negative charges transmitted through its electrodes placed on the skin. The current and the voltage of the electrodes can be adjusted separately in both leads. Subsequently, these 'knocked out' ions are channelled into the porotic bones with the help of the 3rd-reference-electrode. RESULTS: In our preliminary in vitro studies, we used porcine tissues to test their calcium and phosphate content after iontophoresis; with or without using molecules. This preliminary analysis revealed that both calcium and phosphate ions became incorporated into the bone. Some in vivo data are also presented. Iontophoretic treatment increased speed of sound (SOS) as determined by ultrasonography in ovariectomized rats. CONCLUSION: Our results suggest that topical iontophoresis may be suitable to treat local osteoporosis or bone defects.