Benign fasciculation syndrome and migraine aura without headache as possible adverse events after BNT162b2 mRNA vaccination: a web-based survey.

AIM: To determine the characteristics of patients who experienced muscle fasciculations and migraine auras without headache after BNT162b2 immunization. METHODS: In January 2022, we published a case report that described a 48-year-old female patient who experienced muscle twitching and migraine auras without headache following BNT162b2 immunization. A self-administered online survey was sent to people who had written to us and complained of similar symptoms described in the case report (N=20). RESULTS: The survey was completed by 11 participants, of whom 10 reported muscle twitching following BNT162b2 immunization lasting a median of 14 (4-36.5) days. Five of these participants (50%) reported migraine auras without headache. Participants further reported on self-identified triggers that altered the intensity of their symptoms, such as anxiety or caffeine. Fifty percent of participants who got an acute SARS-CoV-2 infection (3/6) experienced increased muscle symptom intensity during the acute phase of the disease. CONCLUSION: To the best of our knowledge, our survey is the first to summarize patients' experiences of these phenomena occurring after BNT162b2 immunization. It is important to note that no causal relationship between vaccination and these phenomena can be inferred.

The Role of ADAMTS-4 in Atherosclerosis and Vessel Wall Abnormalities.

Extracellular matrix proteins are regulated by metzincin proteases, like the disintegrin metalloproteinases with thrombospondin motifs (ADAMTS) family members. This review focuses on the emerging role which ADAMTS-4 might play in vascular pathology, which has implications for atherosclerosis and vessel wall abnormalities, as well as for the resulting diseases, such as cardiovascular and cerebrovascular disease, aortic aneurysms, and dissections. Major substrates of ADAMTS-4 are proteoglycans expressed physiologically in smooth muscle cells of blood vessels. Good examples are versican and aggrecan, principal vessel wall proteoglycans that are targeted by ADAMTS-4, driving blood vessel atrophy, which is why this metzincin protease was implicated in the pathophysiology of vascular diseases with an atherosclerotic background. Despite emerging evidence, it is important not to exaggerate the role of ADAMTS-4 as it is likely only a small piece of the complex atherosclerosis puzzle and one that could be functionally redundant due to its high structural similarity to other ADAMTS family members. The therapeutic potential of inhibiting ADAMTS-4 to halt the progression of vascular disease after initialization of treatment is unlikely. However, it is not excluded that it might find a purpose as a biomarker of vascular disease, possibly as an indicator in a larger cytokine panel.

ADAMTS-4 as a possible distinguishing indicator between osteoarthritis and haemophilic arthropathy.

INTRODUCTION: Osteoarthritis (OA) and haemophilic arthropathy (HA) are clinically similar, but pathologically distinct conditions which result in joint pain and loss of function. Distinguishing their disease mechanisms is therefore a key step in the development of curative therapy, as opposed to current symptomatic treatments. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 4 is a metzincin-family member proteoglycan with known local involvement in OA pathogenesis. AIM: To investigate the potential differences and discriminatory potential of ADAMTS-4 between OA and HA patients. METHODS: We determined ADAMTS-4 plasma concentrations by ELISA in patients with HA and OA. This pilot cross-sectional study included N = 40 male participants equally divided across four subgroups: haemophilia patients with severe or mild HA and control subjects with severe or mild/no OA. RESULTS: Our study showed a striking elevation in plasma ADAMTS-4 expression levels in HA patients as compared to OA, as well as an increase in patients with severe as compared to mild HA. By performing the binomial logistical analysis and fitting the receiver-operator curve (ROC) (cut-off probability .5), ADAMTS-4 had a sensitivity of 95% and specificity of 50% in discriminating between HA and OA among our study participants. CONCLUSION: Uncovering the marked differences in plasma levels of ADAMTS-4 in patients with HA versus OA potentially sheds new light on the mechanisms of HA pathogenesis and could foster more research into the roles ADAMTS-4 and other matrix metalloproteinases (MMPs) play in HA versus OA.

BMP3 Affects Cortical and Trabecular Long Bone Development in Mice.

Bone morphogenetic proteins (BMPs) have a major role in tissue development. BMP3 is synthesized in osteocytes and mature osteoblasts and has an antagonistic effect on other BMPs in bone tissue. The main aim of this study was to fully characterize cortical bone and trabecular bone of long bones in both male and female Bmp3-/- mice. To investigate the effect of Bmp3 from birth to maturity, we compared Bmp3-/- mice with wild-type littermates at the following stages of postnatal development: 1 day (P0), 2 weeks (P14), 8 weeks and 16 weeks of age. Bmp3 deletion was confirmed using X-gal staining in P0 animals. Cartilage and bone tissue were examined in P14 animals using Alcian Blue/Alizarin Red staining. Detailed long bone analysis was performed in 8-week-old and 16-week-old animals using micro-CT. The Bmp3 reporter signal was localized in bone tissue, hair follicles, and lungs. Bone mineralization at 2 weeks of age was increased in long bones of Bmp3-/- mice. Bmp3 deletion was shown to affect the skeleton until adulthood, where increased cortical and trabecular bone parameters were found in young and adult mice of both sexes, while delayed mineralization of the epiphyseal growth plate was found in adult Bmp3-/- mice.

Post-COVID-19 exacerbation of fibrodysplasia ossificans progressiva with multiple flare-ups and extensive heterotopic ossification in a 45-year-old female patient.

Fibrodyplasia ossificans progressiva (FOP) is a rare hereditary disease, which has a variable course characterized by occasional flare-ups of heterotopic ossification (HO) in soft tissues that are followed by swelling, stiffness, pain and warmth. Here, we report for the first time a case of a 45-year-old female patient with known FOP recovering from COVID-19 with disease progression potentially linked with the viral illness. In December 2020 the patient contracted a mild form of COVID-19 infection without need for hospital admission. Since January 2021, the patient felt unwell, with occasional abdominal pain which progressively intensified. In March 2021 she presented with new onset of HO, complaining of pain, swelling and thickening sensation in the lower abdomen and left part of the neck. Computerized tomography (CT) and cytokine analysis were performed. CT scan revealed new heterotopic bone formation in multiple soft tissue areas of the neck indicating clear radiological progression. Radiotherapy, which has proven to be an efficient tool to control HO in this patient, was not able to halt HO formation after COVID-19 infection. Cytokine analysis of a plasma sample obtained during a flare-up after COVID-19 infection showed a significantly elevated pro-inflammatory cytokines compared to a flare-up panel prior to infection. Of the 23 analyzed levels of cytokines, a staggering number of 21 were above normal levels. This case is the first confirmation of uncontrolled post-COVID-19 effects in a FOP patient, which manifested with flare-ups followed by progressive HO, possibly caused by a thus far, never described form of post-COVID syndrome.

Plasma levels of soluble TGF ß receptor type III: no apparent promise as a marker in acute pancreatitis.

AIM: To assess the potential of the soluble transforming growth factor ß receptor type III (sTGFßrIII), a key regulator in TGFß signaling, as a biomarker for diagnosis and stratification of patients with acute pancreatitis (AP). METHODS: In this small prospective pilot study, patients' (N=22) plasma samples were obtained at three time points: the first and fourth day of hospitalization and the day of hospital discharge. Healthy controls' plasma (N=25) was obtained at a single time point. Concentration of sTGFßrIII in plasma was determined by ELISA. Data were analyzed by fitting linear or linear mixed models. RESULTS: Plasma sTGFßrIII levels at presentation (day 1) were similar in AP patients and healthy participants, irrespectively of the disease severity. sTGFßrIII levels in patients were constant during hospital stay. CONCLUSION: These observations do not support further evaluation of plasma sTGFßrIII levels in this setting, but do not exclude a potential biological role of TGFß and membrane-bound TGFßrIII in AP pathophysiology.

Plasma levels and tissue expression of soluble TGFßrIII receptor in women with early-stage breast cancer and in healthy women: a prospective observational study.

BACKGROUND: Mammary carcinogenesis is partly regulated by the transforming growth factor beta (TGFß) signaling pathway. Its function in cancer progression and metastasis is highly dependent on disease stage, and it is likely modulated by the ratio of membrane-bound vs. soluble TGFßrIII (sTGFßrIII). In this prospective observational study, we assessed tissue expression and plasma levels of sTGFßrIII in healthy women, women with benign breast lesions and in early-stage breast cancer patients. METHODS: In a preliminary study, plasma sTGFßrIII levels were determined in 13 healthy women (age 19-40 years) at different phases of the ovarian cycle, and in 15 patients (age 35-75 years) at different times of the day. The main study assessed plasma concentrations of sTGFßrIII in: (i) 158 healthy women in whom breast lesions were excluded; (ii) 65 women with benign breast lesions; (iii) 147 women with newly diagnosed breast cancer classified as American Joint Committee on Cancer (AJCC) stages 0 to IIB. Completers provided blood samples before surgery and at 10-30 and 160-180 days after surgery. Plasma sTGFßrIII concentrations were determined using an indirect ELISA kit. Part of the removed tissues underwent immunohistochemical (IHC) staining and analysis of tissue TGFßrIII expression. RESULTS: There appeared no relevant variations in plasma sTGFßrIII levels at different times of the day or different ovarian cycle phases. Before surgery, breast cancer patients had somewhat higher sTGFßrIII than healthy women, or those with benign breast lesions (by 14.5 and 26 ng/mL, respectively), with a tendency of larger differences at higher age. This correlated with lower expression of TGFßrIII in breast cancer vs. healthy tissue samples. At 160-180 days after surgery, plasma sTGFßrIII levels in breast cancer patients declined by 23-26 ng/mL. CONCLUSIONS: Plasma sTGFßrIII levels do not seem to relevantly vary during the day or the ovarian cycle. The coinciding higher plasma levels in newly diagnosed cancer patients than in healthy subjects and lower TGFßrIII expression in the malignant than in healthy breast tissue suggest ectodomain shedding as a source of circulating sTGFßrIII. Decline in plasma levels after tumor removal supports such a view.

THE ROLE OF NEW TECHNOLOGIES IN DEFINING SALIVARY PROTEIN COMPOSITION FOLLOWING PLACEMENT OF FIXED ORTHODONTIC APPLIANCES - BREAKTHROUGH IN THE DEVELOPMENT OF NOVEL DIAGNOSTIC AND THERAPEUTIC PROCEDURES.

Human saliva is rich in proteins of variable functions (e.g., enzymes, immunoglobulins, cytokines) and origin (blood plasma, salivary glands, or oral microflora). Circadian dynamics, volume and composition (electrolytes, pH, protein, etc.) of secreted saliva vary with local and systemic physiological and pathophysiological conditions. Therefore, the composition of saliva, protein in particular, has been intensively investigated to identify the potential markers and/or mechanisms of systemic and local diseases. Proteomic techniques used for the analysis of biological fluids have enabled great advances in salivary protein stabilization (as the main precondition for their analysis) and detection of those found in saliva in very low concentrations, including small proteins and peptides. This review brings the main characteristics of current proteomic techniques such as liquid chromatography-mass spectrometry, two-dimensional electrophoresis-mass spectrometry, and surface-enhanced laser desorption ionization/time of flight/mass spectrometry. These techniques enable simultaneous identification of hundreds and thousands of protein molecules, as well as identifying those of a potential biological value in particular states. This literature review is focused on the state-of-the-art and possibilities offered by proteomic techniques in analyzing the effects of orthodontic appliances on salivary protein composition and searching for potential markers of therapeutic success/failure or for the molecules by which therapeutic effects are achieved.

Anatomical variations of the frontal sinus and its relationship with the orbital cavity.

The anatomy of the frontal sinus is highly variable and its variations affect the occurrence/course of pathological processes. We investigated its size and relationship to the orbit, searching for patterns that would allow it to be classified anatomically. Cone beam computed tomography was applied to 91 skulls (age range 21-86 years) to determine sinus height, width, length, and length of contact with the orbit in the coronal and sagittal planes. In addition, orbital roof pneumatization in the coronal plane was categorized as: none; only medial part pneumatized; the medial and a portion of the central part pneumatized; roof predominantly pneumatized. Sinus dimensions varied widely (mm): height 6.2-50.0; width 3.7-54.0; length 2.4-45.0; frontal orbital contact 4.0-41.6; sagittal orbital contact 0.0-41.2. Pneumatization of the orbital roof (coronal plane) mostly affected the medial and a portion of the central part (50%), or the roof was predominantly pneumatized (32%). Three "types" of sinus (cluster analysis) were distinguished by the extent of pneumatization of the orbital roof in the coronal plane: "small", pneumatization absent or only of the medial part; "medium-sized", pneumatization of the medial and a portion of the central part; "large", roof predominantly pneumatized. All dimensions were significantly different among the types (P < 0.001). Sinus type was fairly predictive of the extent of contact with the orbit in the sagittal plane (not routinely assessed clinically). The data confirm the variability of frontal sinus anatomy and suggest a simple and straightforward classification with potential clinical relevance. Clin. Anat. 31:576-582, 2018. © 2017 Wiley Periodicals, Inc.

Bone morphogenetic proteins in fracture repair.

Bone fractures represent a significant medical morbidity among aged population with osteoporosis. Bone morphogenetic proteins (BMPs) are suggested to have therapeutic potential to enhance fracture healing in such patients. Though BMP-mediated fracture healing has been well-documented in preclinical models, there has been no clinical study that demonstrated unequivocally that indeed a BMP when presented with an appropriate scaffold could provide basis for robust outcome for delayed or non-union diaphyseal bone fractures. This review presents a comprehensive insight towards the existing knowledge on the role of BMP signaling in bone formation and maintenance. Also therapeutic options based on BMP biology are discussed.A novel osteoinductive autologous bone graft substitute (ABGS) aimed to accelerate bone regeneration was developed and is currently being tested in the clinical setting. It comprises of a biologically compatible autologous carrier made from the patient's peripheral blood (autologous blood coagulum, ABC) and of rhBMP6 as an active ingredient. Such formulation circumvents the use of animal-derived materials, significantly limits inflammatory processes common in commercial bone devices and renders the carrier flexible, malleable, and injectable ensuring the ease of use. The ongoing clinical trials result will provide more detailed insights into the safety, tolerability, pharmacokinetics, and bone healing effects in humans and potentially provide novel and safe therapeutic options for bone repair.

PALMARIS LONGUS ABSENT IN ONE IDENTICAL TWIN: A CASE REPORT.

- Palmaris longus is a very variable muscle in the human body, but it is often used as an applicable tendon graft. We report on differences between one pair of identical twins regarding the existence of the palmaris longus, which were detected accidentally during examination of the presence/absence of this muscle in Caucasian population. In one of the twins, the palmaris longus was present at both forearms, while the other twin was lacking this muscle at both forearms. On search of the available literature, we found no articles about distinctions in the presence or absence of the palmaris longus in twins.

Systemic inhibition of BMP1-3 decreases progression of CCl4-induced liver fibrosis in rats.

Liver fibrosis is a progressive pathological process resulting in an accumulation of excess extracellular matrix proteins. We discovered that bone morphogenetic protein 1-3 (BMP1-3), an isoform of the metalloproteinase Bmp1 gene, circulates in the plasma of healthy volunteers and its neutralization decreases the progression of chronic kidney disease in 5/6 nephrectomized rats. Here, we investigated the potential role of BMP1-3 in a chronic liver disease. Rats with carbon tetrachloride (CCl4)-induced liver fibrosis were treated with monoclonal anti-BMP1-3 antibodies. Treatment with anti-BMP1-3 antibodies dose-dependently lowered the amount of collagen type I, downregulated the expression of Tgfb1, Itgb6, Col1a1, and Acta2 and upregulated the expression of Ctgf, Itgb1, and Dcn. Mehanistically, BMP1-3 inhibition decreased the plasma levels of transforming growth factor beta 1(TGFß1) by prevention of its activation and lowered the prodecorin production further suppressing the TGFß1 profibrotic effect. Our results suggest that BMP1-3 inhibitors have significant potential for decreasing the progression of fibrosis in liver cirrhosis.

Marshall R. Urist and the discovery of bone morphogenetic proteins.

Over the last 40 years International Orthopaedics has published a series of articles on bone morphogenetic proteins (BMPs) covering topics from basic research to clinical applications. This includes also work submitted from the Laboratory for Mineralized Tissues of the School of Medicine University of Zagreb. Accordingly, we felt obliged to give a short summary of Dr. Urist's life and work as our gratitude to his discovery that demineralized bone matrix (DBM) activity induces bone when implanted ectopically into the muscle or under the skin due to bone inducing proteins, named BMPs.

Soluble type III TGFß receptor in diagnosis and follow-up of patients with breast cancer.

Type III transforming growth factor (TGFß) receptor (TGFßrIII) modulates TGFß superfamily signaling. Its tumor tissue expression is downregulated in human breast cancer. We determined (indirect ELISA) plasma levels of the soluble receptor (sTGFßrIII) in 47 women with breast cancer (AJCC stages 0-IIB) (cases) pre-surgery and over two months after the surgery, and in 36 healthy women (controls). Plasma sTBFßrIII was lower in cases than in the controls (age-adjusted difference -29.7 ng/mL, p < 0.001), and discriminated between disease and health (sensitivity and specificity 100% at 16.6 ng/mL). With adjustment for age, AJCC stage, lymph node involvement, HER2 and hormone receptor status, higher pre-surgery sTBFßrIII was associated with better progression-free survival (HR = 0.68, 95%CI 0.49-0.89, p = 0.004). An increasing trend in plasma sTBFßrIII was observed over 2 months after the surgery (0.6% increase/day, p < 0.001), consistently across the patient subsets. Data suggest a high potential of plasma sTBFßrIII as a novel diagnostic and prognostic biomarker in breast cancer.

Biological aspects of segmental bone defects management.

Segmental bone defect management is among the most demanding issues in orthopaedics and there is a great medical need for establishing an appropriate treatment option. Tissue transfer, including bone autografts or free flaps, depending on the size of the bone deficiency, is currently the "gold standard" for treatment of such defects. Osteogenic cells in combination with adequate growth factors and a suitable scaffold, from the aspect of osteoinductivity, osteoconductivity and mechanical stability, are mandatory to successfully restore a bone defect as determined in the "diamond concept". Our current knowledge on this topic is limited and mostly based on retrospective studies, case reports and a few small randomised clinical trials due to the lack of large and accurately designed randomised clinical trials using novel approaches to regenerative orthopaedics. However, preclinical research on different animal models for critical size defects is abundant, showing emerging candidate cells and cytokines for defect rebridgement. In this article we provide an overview on existing clinical studies and promising preclinical experiments that utilised osteogenic cells, growth factors and biomaterials, as well as their combination for repair of segmental bone defects.

Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice.

PURPOSE: Iron overload accelerates bone loss in mice lacking the bone morphogenetic protein 6 (Bmp6) gene, which is the key endogenous regulator of hepcidin, iron homeostasis gene. We investigated involvement of other BMPs in preventing haemochromatosis and subsequent osteopenia in Bmp6-/- mice. METHODS: Iron-treated wild-type (WT) and Bmp6-/- mice were analysed for hepcidin messenger RNA (mRNA) and tissue and blood BMP levels by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR), immunohistochemistry, Western blot, enzyme-linked immunosorbent assay (ELISA) and proximity extension assay. BMPs labeled with technetium-99m were used in pharmacokinetic studies. RESULTS: In WT mice, 4 h following iron challenge, liver Bmp6 and hepcidin expression were increased, while expression of other Bmps was not affected. In parallel, we provided the first evidence that BMP6 circulates in WT mice and that iron increased the BMP6 serum level and the specific liver uptake of (99m)Tc-BMP6. In Bmp6-/- mice, iron challenge led to blunted activation of liver Smad signaling and hepcidin expression with a delay of 24 h, associated with increased Bmp5 and Bmp7 expression and increased Bmp2, 4, 5 and 9 expression in the duodenum. Liver Bmp7 expression and increased circulating BMP9 eventually contributed to the late hepcidin response. This was further supported by exogenous BMP7 therapy resulting in an effective hepcidin expression followed by a rapid normalisation of plasma iron values and restored osteopenia in Bmp6-/- mice. CONCLUSION: In Bmp6-/- mice, iron activated endogenous compensatory mechanisms of other BMPs that were not sufficient for preventing hemochromatosis and bone loss. Administration of exogenous BMP7 was effective in correcting the plasma iron level and bone loss, indicating that BMP6 is an essential but not exclusive in vivo regulator of iron homeostasis.

Systemically available bone morphogenetic protein two and seven affect bone metabolism.

PURPOSE: Bone morphogenetic protein (BMP)-2 and -7 are used in patients with long-bone fractures, nonunions and spinal fusions. It is unknown whether their potential systemic bioavailability following local bone administration might affect skeletal metabolism. To answer this question, we examined effects of systemically administered BMP-2 and -7 on bone in a newly developed rat model with a low level of calciotropic hormones. METHODS: Removal of thyroid and parathyroid glands (TPTx) in rats resulted in a decreased level of calciotropic hormones and subsequent bone loss assessed by micro computed tomography (micro-CT) and measurement of serum bone formation and resorption markers, including osteocalcin, C-telopeptide, osteoprotegerin and receptor activator of nuclear factor kappa-B ligand. Results were complemented with in vitro studies on osteoblast and osteoclast activity by both BMP-2 and -7. The doses used were calculated from published pharmacodynamic studies and bioavailability results from preclinical BMP-2 and -7 studies. RESULTS: TPTx resulted in bone loss, which was restored by systemic administration of 10-70 µg/kg of BMP-2 and 10-250 µg/kg of BMP-7. BMP-2 showed a higher capacity for enhancing trabecular microarchitecture, whereas BMP-7 augmented trabecular thickness. In vitro experiments revealed that BMP-2 and -7 when uncoupled increased the number and activity of both osteoblasts and osteoclasts. CONCLUSIONS: Surprisingly, both BMP-2 and -7 showed an increased bone volume in an in vivo environment of low calciotropic hormones. Locally administered BMP-2 and -7 from bone devices might become partially available in circulation but will not mediate systemic bone loss.

The clinical use of bone morphogenetic proteins revisited: a novel biocompatible carrier device OSTEOGROW for bone healing.

PURPOSE: The purpose of this study was to revise the clinical use of commercial BMP2 (Infuse) and BMP7 (Osigraft) based bone devices and explore the mechanism of action and efficacy of low BMP6 doses in a novel whole blood biocompatible device OSTEOGROW. METHODS: Complications from the clinical use of BMP2 and BMP7 have been systemically reviewed in light of their role in bone remodeling. BMP6 function has been assessed in Bmp6-/- mice by µCT and skeletal histology, and has also been examined in mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and osteoclasts. Safety and efficacy of OSTEOGROW have been assessed in rats and rabbits. RESULTS: Clinical use issues of BMP2 and BMP7 have been ascribed to the limited understanding of their role in bone remodeling at the time of device development for clinical trials. BMP2 and BMP7 in bone devices significantly promote bone resorption leading to osteolysis at the endosteal surfaces, while in parallel stimulating exuberant bone formation in surrounding tissues. Unbound BMP2 and BMP7 in bone devices precipitate on the bovine collagen and cause inflammation and swelling. OSTEOGROW required small amounts of BMP6, applied in a biocompatible blood coagulum carrier, for stimulating differentiation of MSCs and accelerated healing of critical size bone defects in animals, without bone resorption and inflammation. BMP6 decreased the number of osteoclasts derived from HSC, while BMP2 and BMP7 increased their number. CONCLUSIONS: Current issues and challenges with commercial bone devices may be resolved by using novel BMP6 biocompatible device OSTEOGROW, which will be clinically tested in metaphyseal bone fractures, compartments where BMP2 and BMP7 have not been effective.

Dynamics of optic canal and orbital cavity development revealed by microCT.

PURPOSE: Numerous studies have attempted to clarify the exact anatomy and variations of the optic canal with non-conclusive results due to its close proximity to many vulnerable structures. We sought to determine the dynamics of growth and development of these structures on fetal skulls, which will help us to better understand of gender and age-dependent variations, as well as fatal malformations. METHODS: Fifteen previously macerated fetal frontal and sphenoid bones were analyzed and the diameters of optic canal, and distance of orbit from frontomaxillary suture to frontozygomatic suture were measured using 3D reconstruction images obtained by micro-CT. RESULTS: Average diameter of the optic canal in 300 mm fetus was measured to be 1,546 ± 36 µm, in 400 mm fetus 2,470 ± 123 µm and in 500 mm fetus 3,757 ± 203 µm. This trend indicates a linear enlargement of optic canal during the fetal period. During the same time period, diameter of the orbit enlarges from 12,319 ± 559 µm in 300 mm fetus to 19,788 ± 736 µm in 500 mm fetus. Growth curve is significantly lower in comparison with the same curve in optic canal data. We also calculated the ratio of orbit diameter and optic canal diameter between those groups which decreased from a value of 7.9 ± 0.4 for 300 mm fetus to 5.3 ± 0.2 for 500 mm fetus. CONCLUSION: Dynamics of optic canal and orbital cavity development is different in early and late fetal period. Diameters of those structures are in better correlation with the fetal length.