The osteogenic and mineralogenic potential of the microalgae Skeletonema costatum and Tetraselmis striata CTP4 in fish models.

Skeletal disorders are problematic aspects for the aquaculture industry as skeletal deformities, which affect most species of farmed fish, increase production costs and affect fish welfare. Following recent findings that show the presence of osteoactive compounds in marine organisms, we evaluated the osteogenic and mineralogenic potential of commercially available microalgae strains Skeletonema costatum and Tetraselmis striata CTP4 in several fish systems. Ethanolic extracts increased extracellular matrix mineralization in gilthead seabream (Sparus aurata) bone-derived cell cultures and promoted osteoblastic differentiation in zebrafish (Danio rerio) larvae. Long-term dietary exposure to both extracts increased bone mineralization in zebrafish and upregulated the expression of genes involved in bone formation (sp7, col1a1a, oc1, and oc2), bone remodeling (acp5a), and antioxidant defenses (cat, sod1). Extracts also improved the skeletal status of zebrafish juveniles by reducing the incidence of skeletal anomalies. Our results indicate that both strains of microalgae contain osteogenic and mineralogenic compounds, and that ethanolic extracts have the potential for an application in the aquaculture sector as dietary supplements to support fish bone health. Future studies should also identify osteoactive compounds and establish whether they can be used in human health to broaden the therapeutic options for bone erosive disorders such as osteoporosis.

Supplementary orthopaedic screening for children and adolescents to prevent permanent skeletal deformities - protocol for the "OrthoKids" study.

BACKGROUND: Skeletal deformities (SD) in children and adolescents can lead to arthritic conditions, impairment of quality of life, and high treatment costs in the long term. However, comprehensive data on the prevalence of SDs in children and adolescents are limited and it remains therefore unclear whether there is a healthcare gap. "OrthoKids" is a project that addresses this evidence gap by implementing an orthopaedic screening for children and adolescents that supplements existing detection examinations within statutory standard care in Germany. OBJECTIVE: To detect SDs so that they can be treated as needed at an early stage. METHODS: The implementation of the supplementary orthopaedic screening will be evaluated through an exploratory cohort study that is set up in the German state Baden-Wuerttemberg. 20,000 children and adolescents aged 10 to 14 years will be recruited as a prospective cohort. A retrospective control cohort will be formed based on claims data provided by two cooperating statutory health insurances (SHIs). Participating children and adolescents receive a one-time orthopaedic screening. If at least one SD is diagnosed, treatment will be provided as part of the statutory standard care. Within the scope of the project, a follow-up examination will be performed after one year. An IT-platform will complement the study. The primary outcome measure is the point prevalence of scoliosis, genu varum/valgum, hip dysplasia, and flat feet. Secondary outcome measures are (i) the point prevalence of further less common SDs, (ii) health-related quality of life (HRQoL), (iii) sports ability based on activity (physical/athletic), physical constraints, and (sports) injuries, as well as (iv) monetary consequences of the orthopaedic screenings' implementation. Implementation determinants will be evaluated, too. DISCUSSION: If the supplementary orthopaedic screening proves to be viable, it could be considered as a supplementary examination for children and adolescents within the frame of SHI in Germany. This could relieve the burden of disease among children and adolescents with SDs. In addition, it could disburden SHIs in the medium to long term. TRIAL REGISTRATION: The OrthoKids study was registered in the German Clinical Trials Registry (Deutsches Register Klinischer Studien (DRKS)) on 26th July 2022 under the number 00029057.

Clinical, radiographic and molecular characterization of two unrelated families with multicentric osteolysis, nodulosis, and arthropathy.

BACKGROUND: Multicentric osteolysis nodulosis and arthropathy (MONA) is a rare autosomal recessive disorder characterized by marked progressive bone loss and joint destruction resulting in skeletal deformities. MONA is caused by MMP2 deficiency. Here we report clinical and molecular analyses of four patients in two families from Pakistan and Finland. METHODS: Clinical analyses including radiography were completed and blood samples were collected. The extracted DNA was subjected to whole-exome analysis or target gene sequencing. Segregation analyses were performed in the nuclear pedigree. Pathogenicity prediction scores for the selected variants and conservation analyses of affected amino acids were observed. RESULTS: The phenotype in the four affected individuals was consistent with multicentric osteolysis or MONA, as the patients had multiple affected joints, osteolysis of hands and feet, immobility of knee joint and progressive bone loss. Long-term follow up of the patients revealed the progression of the disease. We found a novel MMP2 c.1336 + 2T > G homozygous splice donor variant segregating with the phenotype in the Pakistani family while a MMP2 missense variant c.1188 C > A, p.(Ser396Arg) was homozygous in both Finnish patients. In-silico analysis predicted that the splicing variant may eventually introduce a premature stop codon in MMP2. Molecular modeling for the p.(Ser396Arg) variant suggested that the change may disturb MMP2 collagen-binding region. CONCLUSION: Our findings expand the genetic spectrum of Multicentric osteolysis nodulosis and arthropathy. We also suggest that the age of onset of this disorder may vary from childhood up to late adolescence and that a significant degree of intrafamilial variability may be present.

Skeletal deformities and meristic trait variations are common in the intertidal fish Bathygobius cocosensis (Perciformes-Gobiidae).

Extreme environmental conditions, such as temperature, can lead to meristic trait variation and skeletal deformities, which may have major impacts on individual fitness. As intertidal ecosystems experience rapid temperature and physicochemical fluctuations, intertidal fish living and reproducing in these environmental conditions may have phenotypes influenced by such variable environments. The impact of intertidal variability on fish development, however, has not been previously investigated. Skeletal deformities and meristic traits were assessed for Bathygobius cocosensis, a common intertidal fish living across the Indo-Pacific region, using a clearing and staining method on 72 individuals. Over 87% of individuals presented meristic variation and over 70% exhibited at least one type of skeletal deformity, mostly recorded in the caudal fin area. The unexpected prevalence of skeletal deformities among this intertidal fish population suggests that such deformities may be suitable markers to evaluate an individual's stress exposure during development and the subsequent fitness effects.

Cone-Beam Computed Tomography Evaluation of Skeletal Deformities and Pharyngeal Airway in Chinese Han Individuals With Nonsyndromic Unilateral Cleft Lip and Palate.

OBJECTIVE: This study examined the relationships between skeletal deformities and the pharyngeal airway of patients with nonsyndromic unilateral cleft lip and palate (UCLP). DESIGN: Retrospective study. SETTING: Orthodontics and Oral and Maxillofacial Surgery Departments in the Affiliated Hospital of Stomatology, Nanjing Medical University, China. PATIENTS, PARTICIPANTS: The sample comprised 30 nonsyndromic UCLP patients and 30 healthy controls. Each group has 23 males and 7 females. INTERVENTIONS: All cone-beam computed tomography images were obtained with the participant in the standard supine position and asked to bite with intercuspal position without swallowing or moving their heads and tongues during scanning. MAIN OUTCOME MEASURE(S): SNA, SNB, ANB, anterior cranial base, Wits appraisal, maxillary length (PTM-ANS || FH), maxillary position (S-PTM || FH), mandibular length (Go-Pog || MP), FMA, posterior face height, anterior face height, Posterior-Anterior face height, lower face height, pharyngeal airway volumes, and areas were evaluated by Dolphin imaging software. RESULTS: The UCLP group showed significantly decreased SNA, SNB, ANB, PTM-ANS || FH, S-PTM || FH, P-A Face Height compared with the controls. However, the airway volumes and areas showed no significant difference between 2 groups. The total airway volume and minimum cross-sectional area in UCLP patients were related to the Go-Pog || MP and FMA. CONCLUSIONS: Patients with UCLP have both the maxillary and mandibular deficiencies in the sagittal dimension. Both the sagittal and vertical relationships of the jaw might affect the airway volume and area. However, no significant difference was detected in airway volume and area in UCLP patients when compared with the controls.

Osteotoxicity of 3-methylcholanthrene in fish.

Many chemicals produced by human activities end up in the aquatic ecosystem causing adverse developmental and reproductive effects in aquatic organisms. There is evidence that some anthropogenic chemicals disturb bone formation and skeletal development but the lack of suitable in vitro and in vivo systems for testing has hindered the identification of underlying mechanisms of osteotoxicity. Several fish systems - an in vitro cell system to study extracellular matrix mineralization and in vivo systems to evaluate bone formation and skeletogenesis - were combined to collect data on the osteotoxic activity of 3-methylcholanthrene (3-MC), a polycyclic aromatic hydrocarbon. Anti-mineralogenic effects, increased incidence of skeletal deformities and reduced bone formation and regeneration were observed in zebrafish upon exposure to 3-MC. Pathway reporter array revealed the role of the aryl hydrocarbon receptor 2 (Ahr2) in the mechanisms underlying 3-MC osteotoxicity in mineralogenic cell lines. Analysis of gene expression in zebrafish larvae confirmed the role of Ahr2 in the signaling of 3-MC toxicity. It also indicated a possible complementary action of the pregnane X receptor (Pxr) in the regulation of genes involved in bone cell activity and differentiation but also in xenobiotic metabolism. Data reported here demonstrated the osteotoxicity of 3-MC but also confirmed the suitability of fish systems to gain insights into the toxic mechanisms of compounds affecting skeletal and bone formation.

PRELIMINARY RADIOGRAPHIC OBSERVATIONS OF VERTEBRAL CHANGES IN DISCUS ( SYMPHYSODON DISCUS).

Discus ( Symphysodon discus) maintained in aquaria are held in a wide range of water parameters and subjected to many different feeding regimes. In a pilot study, four groups of discus (mean length 12.1 cm, mean weight 57.3 g) were submitted to a radiographic examination to assess the skeletal structure of the vertebral column under defined environmental conditions. Water temperature was 30°C for all groups. Two groups were held at <28.6 mg/L calcium (Ca) and two at 50.0-78.6 mg/L Ca within the ambient water. One of each water quality group was fed a commercial discus diet while the other two groups were kept on a plain beef-heart diet, creating a total of four separate groups. In the case of the beef heart group, dietary Ca content (g/kg) was 0.06 and phosphorous (P) content 2.06, leading to a Ca : P ratio of 0.03, whereas in the commercial diet group a Ca content of 20.1 g/kg and P of 7.36 g/kg resulted in a Ca : P ratio of 2.7. Magnesium (Mg) contents of the beef-heart diet were 0.21 and of the commercial diet 1.69 g/kg. Six fish were submitted to radiography at the beginning of the experiment as a control. After 16 wk of the above diets and environmental conditions, radiographs were taken from all fish (six per group) and evaluated by three independent persons using a scoring system. Alterations were found in all groups. The results of this pilot study give reason to scrutinize rearing and keeping conditions of this fish species.

Defective skeletogenesis and oversized otoliths in fish early stages in a changing ocean.

Early life stages of many marine organisms are being challenged by rising seawater temperature and CO2 concentrations, but their physiological responses to these environmental changes still remain unclear. In the present study, we show that future predictions of ocean warming (+4°C) and acidification (ΔpH=0.5 units) may compromise the development of early life stages of a highly commercial teleost fish, Solea senegalensis. Exposure to future conditions caused a decline in hatching success and larval survival. Growth, metabolic rates and thermal tolerance increased with temperature but decreased under acidified conditions. Hypercapnia and warming amplified the incidence of deformities by 31.5% (including severe deformities such as lordosis, scoliosis and kyphosis), while promoting the occurrence of oversized otoliths (109.3% increase). Smaller larvae with greater skeletal deformities and larger otoliths may face major ecophysiological challenges, which might potentiate substantial declines in adult fish populations, putting in jeopardy the species' fitness under a changing ocean.

A new type of lordosis and vertebral body compression in Gilthead sea bream, Sparus aurata L.: aetiology, anatomy and consequences for survival.

A new type of vertebral malformation is described, consisting of deformed cartilaginous neural and haemal processes and the compression and fusion of vertebral bodies. The malformation is designated as haemal vertebral compression and fusion (haemal VCF). We studied the aetiology of the malformations and described microanatomical histopathological alterations. The malformations were detected during routine quality control in one of six monitored Gilthead sea bream populations. Haemal VCF affected the posterior part of the vertebral column (haemal vertebrae). In 20% of the deformed specimens, haemal VCF was combined with lordosis. At 35 dph (days post-hatching), early anatomical signs of the haemal VCF consisted of abnormal centrum mineralization, malformed cartilaginous neural and haemal processes and developing lordotic alterations. The histological examination of the deformed individuals revealed that haemal VCF is preceded by notochord abnormalities. The frequency of deformed individuals was three times higher at 35 than at 61 dph (50.3% vs. 17.2%, n = 157 and n = 250, respectively). No signs of repair or reversion of malformations have been observed. Thus, the steep decrease in deformities in older animals suggests that haemal VCF is linked to high mortality rates. The results are discussed in respect of the possible causative factors of haemal VCF.

Skeletal maturation in different anteroposterior and vertical skeletal growth patterns in female subjects.

PURPOSE: The aim of the present work was to study the sequence of skeletal maturation in the various anteroposterior and vertical skeletal growth patterns and to detect whether differences existed between them. METHODS: Cephalograms of 861 growing and adolescent female patients were traced to categorize the subjects into 9 skeletal patterns. Each subject was assigned a skeletal maturational stage. Analysis of variance (ANOVA) followed by Bonferroni test were used to detect differences in the onset of the three growth stages (prepubertal, pubertal and postpubertal) between the 9 groups. The same statistical methods were used to detect differences between the mean ages at the three growth stages within each group. RESULTS: No statistically significant differences were found between the mean ages of pubertal and postpubertal growth stages between the 9 skeletal patterns. However, class III growers had a significantly earlier onset of prepubertal growth (10.25 ± 1.56 years) when compared to that of class II high angle cases (11.11 ± 1.67 years; P < 0.01). Also, significant differences were found between the mean ages at the three growth stages within the groups. CONCLUSION: A map was created defining the sequence of skeletal maturation for each skeletal growth pattern. This map defines clinically relevant differences in the starting time points and the optimum intervals of growth modification for each skeletal growth pattern.

Atypical corneal clouding in mucopolysaccharidoses.

The etiology for corneal clouding from the birth is varied and includes conditions such as sclerocornea, birth trauma, corneal ulcer, Peters anomaly, and rare causes like mucopolysaccharidoses (MPS). The lysosomal storage disorders are associated with a varied ocular manifestation including bilateral corneal clouding which is often mild and stippled except in few cases like Hunter syndrome where cornea is often clear. We report a case of MPS Type I S (MPS 1) with near-normal visual acuity and bilateral dense corneal clouding with sparing of central 3 mm of cornea. The patient also had typical facial and skeletal abnormalities of lysosomal storage disorder. To our best knowledge, MPS 1 with marked corneal clouding with sparing of central cornea is very rare and has not been reported. This case report emphasizes on the atypical ocular presentation of MPS and the need for ophthalmological screening in the storage disorders.

A Novel Approach in the Development of Larval Largemouth Bass Micropterus salmoides Diets Using Largemouth Bass Muscle Hydrolysates as the Protein Source.

This study's objectives were to determine the effect of Largemouth Bass (LMB) muscle hydrolysates obtained using same-species digestive enzymes and the degree of LMB muscle hydrolysis when included in the first feeds of growth performance and survival, skeletal development, intestinal peptide uptake, and muscle-free amino acid composition of larval LMB. LMB muscle was mixed with digestive enzymes from adult LMB, and hydrolyzed for 1.5, 3, and 6 h, respectively. Five diets were produced, the intact diet containing non-hydrolyzed muscle and four diets with 37% muscle hydrolysate inclusion. Those diets were characterized by their level of each hydrolysate (presented as a ratio of 1.5, 3, and 6 Ts hydrolysates): 1:1:1, 1:3:6, 1:3:1, 6:3:1 for diets A, B, C, and D, respectively. To account for gut development, one group of larval LMB was fed a weekly series of diets B, C, and D to provide an increasing molecular weight profile throughout development. This group was compared against others that received either; (1) diets D, C, and B; (2) diet A; or (3) intact diet. The initial inclusion of the hydrolysates significantly improved the total length of the larval LMB; however, neither the hydrolysate inclusion nor the series of dietary molecular weight profiles improved the overall growth of larval LMB. The inclusion of hydrolysates significantly decreased the occurrence of skeletal deformities. The degree of hydrolysis did not have a significant effect on the parameters measured, except for intestinal peptide uptake, which was increased in the group that received the most hydrolyzed diet at the final time of sampling. The lack of overall growth improvement suggests that while the hydrolysates improve the initial growth performance, further research is necessary to determine the optimal molecular weight profile, hydrolysate inclusion level, and physical properties of feeds for larval LMB.

Recent Advances in Bioimage Analysis Methods for Detecting Skeletal Deformities in Biomedical and Aquaculture Fish Species.

Detecting skeletal or bone-related deformities in model and aquaculture fish is vital for numerous biomedical studies. In biomedical research, model fish with bone-related disorders are potential indicators of various chemically induced toxins in their environment or poor dietary conditions. In aquaculture, skeletal deformities are affecting fish health, and economic losses are incurred by fish farmers. This survey paper focuses on showcasing the cutting-edge image analysis tools and techniques based on artificial intelligence that are currently applied in the analysis of bone-related deformities in aquaculture and model fish. These methods and tools play a significant role in improving research by automating various aspects of the analysis. This paper also sheds light on some of the hurdles faced when dealing with high-content bioimages and explores potential solutions to overcome these challenges.

Pathophysiological Investigation of Skeletal Deformities of Musculocontractural Ehlers-Danlos Syndrome Using Induced Pluripotent Stem Cells.

Musculocontractural Ehlers-Danlos syndrome caused by mutations in the carbohydrate sulfotransferase 14 gene (mcEDS-CHST14) is a heritable connective tissue disorder characterized by multiple congenital malformations and progressive connective tissue fragility-related manifestations in the cutaneous, skeletal, cardiovascular, visceral, and ocular systems. Progressive skeletal deformities are among the most frequent and serious complications affecting the quality of life and activities of daily living in patients. After establishing induced pluripotent stem cells (iPSCs) from cultured skin fibroblasts of three patients with mcEDS-CHST14, we generated a patient iPSC-based human osteogenesis model and performed an in vitro assessment of the phenotype and pathophysiology of skeletal deformities. Patient-derived iPSCs presented with remarkable downregulation of osteogenic-specific gene expression, less alizarin red staining, and reduced calcium deposition compared with wild-type iPSCs at each stage of osteogenic differentiation, including osteoprogenitor cells, osteoblasts, and osteocytes. These findings indicated that osteogenesis was impaired in mcEDS-CHST14 iPSCs. Moreover, the decrease in decorin (DCN) expression and increase in collagen (COL12A1) expression in patient-derived iPSCs elucidated the contribution of CHST14 dysfunction to skeletal deformities in mcEDS-CHST14. In conclusion, this disease-in-a-dish model provides new insight into the pathophysiology of EDS and may have the potential for personalized gene or drug therapy.

Aloe vera protects against fluoride-induced teratogenic effects during pre- and postnatal development in mice.

Pregnancy and feto-gestational toxicities on exposure to fluoride and its possible amelioration on co-administration with aloe vera were studied in pregnant Swiss albino mice. Once the confirmed pregnancy was tested, animals were equally divided into four groups as follows: group I was given no treatment and served as control, and groups II and III were administered with 100 and 300 ppm sodium fluoride, respectively, while group IV was co- administered aloe vera (300 mg/kg bw) along with sodium fluoride (300 ppm) daily for 14 days prior to gestation and continued till the 18th day of gestation. Animals were sacrificed on the 19th day of gestation for prenatal observations. Maternal body weight, the gravid uterine weight, number of corpora lutea in both the ovaries, number of implantations and resorptions, number of live (mature and immature) fetuses, and number of dead fetuses were examined in each dam. The treatment continued in another set of animals till the completion of the weaning period to observe postnatal changes due to test substances on the mother and pups. Sodium fluoride-treated animals showed morphometric and skeletal changes which were more pronounced in the high-dose group showing significantly decreased body weight gain in pregnant mothers and dead/immature fetuses. Morphometric changes included open eyelids, limb defects, wrinkles on the whole body, anophthalmia, pulmonary edema, enlarged esophagus, and decreased body weight of fetuses and pups. Alizarin-prepared skeletal structures of fetuses of such female mice showed delayed ossification or bending in the number of bones of skull, thoracic, and limb regions. However, concomitant exposure to sodium fluoride and aloe vera in treated animals led to a marked improvement in all the prenatal and postnatal variables. The study suggests that sodium fluoride at high concentrations may be teratogenic while co-administration of aloe vera during fluoride exposure might be beneficial in reducing these toxic effects. The use of aloe vera as a preventive agent or as a complimentary agent is thus recommended following fluoride exposure through the oral route.

Bone deformities in patients with neurofibromatosis type 1: Single-center experience.

BACKGROUND: Neurofibromatosis type 1 (NF-1) is the most common neurocutaneous syndrome with an autosomal dominant inheritance. However, half of the cases are de novo mutations. Involvement of bone, skin (cafe au lait macules), as well as ocular and tumoral formations is also associated with NF-1. Here, we present our case series of patients with bone deformities. METHODS: The medical files of patients with NF-1 who were followed up by the same doctor in the pediatric neurology outpatient clinic over 2 years were retrospectively analyzed. RESULTS: Overall, 19 girls and 13 boys were diagnosed with NF-1. Of these 32 patients, 12 (nine girls, three boys) were found to have bone pathologies. The average age was of these patients with bone pathology was 7.5 and 9.5 years. Scoliosis, bowing, short stature, and long bone cysts were found in descending order of frequency. Severe adhesions in the hands and feet as well as phalangeal hypoplasia were noted in one patient. CONCLUSION: NF-1 requires a multidisciplinary approach. Routine follow-up is very important as it is known that deformities that affect different systems may appear or increase with age. Severe hand and foot anomalies seen in one of our patients did not seem to be associated with NF-1.

Neurogenic Bladder-Induced Stone in a Pelvic Kidney of a Caudal Regression Syndrome Patient: Management of a Complex Case.

Percutaneous nephrolithotomy (PCNL) is a difficult treatment for treating kidney stones, especially when there are orthopedic or skeletal abnormalities. Here, in a 19-year-old male, we describe a two-step PCNL with a case of caudal regression syndrome (CRS) and a pelvic kidney, with an extremely deformed neurogenic bladder on intermittent catheterization. Our conclusion is that PCNL may be done safely with minimum morbidity in patients with caudal regression syndrome by utilizing adult equipment for heavy stone burdens, allowing full and rapid stone removal.

CT and MRI characteristics of presumptive hypervitaminosis A in a cat.

CASE SUMMARY: A rescued stray cat with an unknown history was examined for non-ambulatory paraparesis in the hindlimbs. Survey radiographs revealed typical findings of hypervitaminosis A, characterised by vertebral exostoses and extensive osteophytes, mainly in the cervicothoracic spine. CT findings were consistent with the radiographic findings, and CT-based volume rendering and virtual endoscopy into the vertebral canal were created for three-dimensional visualisation of the lesion. MRI revealed a focal and mild dilation of the central canal of the spinal cord. Although the clinical diagnosis of hypervitaminosis A is based on an unusual dietary history and characteristic radiographic findings, the history of this cat was unknown and serum concentrations of vitamin A were unremarkable, when measured >1 month after rescue. However, other possible differential diagnoses were thought to be unlikely and clinical signs never worsened, and thus, hypervitaminosis A was presumed. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report to present the CT and MRI characteristics of a cat with suspected hypervitaminosis A.

Unicompartmental Knee Arthroplasty for Severe Osteoarthritis and Pseudarthrosis in a Patient with Neurofibromatosis.

We describe the case of a 76-year-old Asian female patient who presented with severe pain and a valgus deformity of the right knee. Her past medical history included neurofibromatosis, which resulted in a severe anterior slope of the right knee, limb shortening, and congenital pseudarthrosis. She was diagnosed with severe anterolateral osteoarthritis and eburnation of the right knee that was treated surgically with a lateral unicompartmental knee arthroplasty (UKA). Bone and cartilage fragments were removed from the joint space and a UKA implant (Zimmer®) with dimensions of 29 mm × 50 mm was inserted. Perioperative imaging revealed that the procedure resulted in the correction of the valgus deformity. Pain was reduced and the patient was able to walk for 10 meters with support during the immediate postoperative period. One week post-surgery, the patient sustained an oblique tibial fracture that extended from the medial edge of the implant to the medial slope of the proximal tibia. This complication may have been attributed to large implant size or sagittal overcutting. The fracture was treated surgically with a rotated anterolateral locking plate (A.L.P.S®) inserted into the distal tibia. The patient was capable of ambulation at full weight load at two months after the second procedure. It is critical to recognize that there are no standard protocols that can be used to guide the treatment of neurofibromatosis-induced osteoarthritis. The specific preoperative condition of the individual patient plays a large role in determining the appropriate treatment option. In this case, the availability of custom-fitted UKA implants might have improved outlook, we understand that these devices are costly and may not be available at all hospitals. However, we strongly believe that the "gold standard" in these cases is patient-specific treatment that addresses the issues of the highest concern using the resources that are available at that time.