Role of fibroblast growth factor-23 as an early marker of metabolic bone disease of prematurity.

PURPOSE: Metabolic bone disease of prematurity (MBDP) remains a significant cause of morbidity in extremely premature newborns. In high-risk patients, suspected diagnosis and subsequent treatment modifications, with limitations in terms of sensitivity and specificity, rely on low phosphorus levels and/or high levels of alkaline phosphatase (ALP). We investigated the potential of fibroblast growth factor-23 (FGF23) as an early marker for MBDP when measured at 3-4 weeks of life in at-risk patients. METHODS: A single-center prospective observational non-interventional study including preterm newborns of both sexes, with a gestational age of less than 32 weeks and/or a birth weight of less than 1500 g. In the standard biochemical screening for MBDP performed between 3 and 4 weeks of life within a nutritional profile, the determination of FGF23 was included along with other clinical and metabolic studies. The study was conducted at Marqués de Valdecilla University Hospital in Santander, Spain, from April 2020 to March 2021. Participants provided informed consent. Biochemical analyses were conducted using various platforms, and follow-up evaluations were performed at the discretion of neonatologists. Patients at high risk for MBDP received modifications in treatment accordingly. The sample was descriptively analyzed, presenting measures of central tendency and dispersion for continuous variables, and absolute numbers/percentages for categorical ones. Tests used included t-tests, Mann‒Whitney U tests, chi-square tests, logistic regressions, Pearson correlation, and ROC curve analysis (IBM SPSS Statistics version 19). Significance level: P < 0.05. RESULTS: In the study involving 25 at-risk premature newborns, it was found that 20% (n = 5) were diagnosed with MBDP. Three of these patients (60%) were identified as high-risk based on standard biochemical evaluation at 3-4 weeks of age, while the other two patients (40%) were diagnosed in subsequent weeks. However, in all 5 patients, measurement of FGF23 levels would allow for early identification and optimization of treatment before other markers become altered. Low levels of FGF23 at 3-4 weeks, even with normal phosphorus and ALP levels, indicate the need for modifications in nutritional supplementation. CONCLUSIONS: MBDP remains a significant concern in extremely premature newborns. Current diagnostic methods rely on limited biochemical markers. Early detection of low FGF23 levels enables timely interventions, potentially averting demineralization.

Thyroid dysgenesis associated with dwarfism, osteoporosis and spontaneous fractures in a goat.

An 11-month-old female Saanen goat, weighing 12.7 kg, was taken to the Veterinary Hospital of the Federal University of Minas Gerais because of sternal recumbency. On clinical examination, the animal was much smaller than expected and had hair similar to that of puppies and areas of hyperpigmentation on the head and dorsocervical and dorsothoracic cranial regions. Radiographic examination revealed fractures in both femurs and severe generalized osteoporosis. Given the unfavourable prognosis, the animal was euthanized. Necropsy revealed generalized pallor, muscular atrophy of the pelvic limbs and little reserve of subcutaneous adipose tissue. Both femurs had complete and closed diaphyseal fractures. The second lumbar vertebra was severely reduced in length as a result of a fracture, with dorsal displacement of the vertebral body towards the vertebral canal and compression of the spinal cord. Long bones and vertebrae had severe cortical thinning, enlargement of the medullary canal and reduced resistance. The thyroid gland was not in its normal anatomical location. A pale red nodule (1.0 × 0.4 cm) in the serosa of the middle third of the trachea, close to the thoracic entrance, was confirmed as ectopic thyroid tissue. Microscopically, the bones had evidence of growth arrest and severe osteoporosis. The ectopic thyroid nodule was hyperplastic with severe hypertrophy of follicular cells. The spinal cord was compressed by vertebral fractures and had focally extensive and severe myelomalacia. Based on the pathological features, the case was diagnosed as thyroid dysgenesis characterized by eutopic thyroid agenesis and ectopic thyroid tissue, associated with interruption of bone growth with dwarfism, osteoporosis and spontaneous secondary fractures with compression of the lumbar spinal cord.

Biomarkers and Biochemical Indicators to Evaluate Bone Metabolism in Preterm Neonates.

The purpose of the present study was to evaluate the concentrations of some bone turnover markers in preterm neonates with uncomplicated clinical course in the first month of life. Samples from 13 preterm neonates were collected at three different times: at birth (T0) from umbilical cord blood (UCB); and at 15 (T1) and 30 (T2) days of life from peripheral blood (PB). The concentrations of calcium (Ca), phosphate (P), total alkaline phosphatase (ALP), Collagen Type 1 Amino-terminal Propeptide (PINP), osteocalcin (OC), Collagen Type 1 Carboxyl-Terminal Telopeptide (CTX) and Leptin were assessed. A statistically significant difference for ALP concentration at birth versus T1 and T2 was found. An evident increase in the median concentrations of CTX, OC and PINP from T0 to T2 were observed. A significant difference was also found for Leptin concentration at T0 compared to T1. In preterm infants, in the absence of acute or chronic medical conditions and without risk factors for metabolic bone disease (MBD) of prematurity, there is a significant increase in bone turnover markers during the first month of life. The knowledge of the variations in these markers in the first weeks of life, integrated by the variations in the biochemical indicators of bone metabolism, could help in recognizing any conditions at risk of developing bone diseases.

Pediatric hypophosphatasia: avoid diagnosis missteps!

Hypophosphatasia (HPP) is the dento-osseous disorder caused by deactivating mutation(s) of ALPL, the gene that encodes the "tissue-nonspecific" isoenzyme of alkaline phosphatase (TNSALP). In HPP, 3 natural substrates of cell-surface TNSALP accumulate extracellularly; phosphoethanolamine (PEA), inorganic pyrophosphate (PPi), and pyridoxal 5'-phosphate (PLP). Hypophosphatasemia together with elevated plasma levels of PEA, PPi, and PLP comprise its biochemical signature. PPi can inhibit mineralization and in extracellular excess can impair bone and tooth hardening and perhaps explain weak muscle. Autosomal dominant or autosomal recessive inheritance from among more than 400 mutations of ALPL largely accounts for HPP's broad-ranging severity, greatest among all skeletal diseases. Pediatric HPP spans life-threatening perinatal and infantile forms, childhood forms, and odonto-HPP selectively featuring premature loss of deciduous teeth. ALPL gene testing and TNSALP supplementation therapy have bolstered familiarity with HPP, but there are new considerations for diagnosis. Herein, diagnosis of a boy's mild childhood HPP was delayed by missteps involving his medical and dental history, physical examination, radiographic findings, and clinical laboratory studies. We review how pediatric HPP is now identified. Prompt diagnosis while appreciating the broad-ranging severity of HPP underlies the safe and effective management of this inborn-error-of-metabolism.

Analysis of clinical risk factors for metabolic bone disease of prematurity.

Objective: To analyze clinical data related to preterm infants and identify risk factors for metabolic bone disease of prematurity (MBDP). Methods: This study involved 856 newborns with a gestational age of less than 37 weeks or a weight of less than 1,500g at the Second Hospital of Jilin University. Multifactorial analysis was performed using logistic regression models to explore the risk factors for MBDP. Linear regression was used to investigate the factors affecting the time of alkaline phosphatase (ALP) exceedance and the peak value of ALP in the MBDP group. Results: In the MBDP group, ALP excesses occurred in preterm infants at an average of 39.33 days after birth, and the mean value of peak ALP was 691.41 IU/L. Parenteral nutrition and the application of assisted ventilation were independent risk factors for MBDP, with ORs of 1.02 and 1.03 respectively. Gestational age was found to be a protective factor for earlier time of onset of ALP exceedance (ß = 2.24,) and the increase in the peak value of ALP (ß = -16.30). Conclusion: Parenteral nutrition and the application of assisted ventilation are independent risk factors for MBDP. Gestational age is a major factor influencing the time of onset of ALP exceedance and the peak value of ALP in infants with MBDP.

European survey showed wide variations in diagnostic procedures and management strategies for metabolic bone disease of prematurity in 22 countries.

AIM: The aim of this study was to evaluate the clinical relevance, diagnostic procedures and treatment strategies for metabolic bone disease in preterm infants across Europe. METHODS: An e-survey was distributed by email to 545 neonatal units in 38 European countries between July and October 2021. The protocol was based on the Checklist for Reporting Results of Internet E-Surveys. RESULTS: In total, 76 neonatal units (14%) from 22 European countries (58%) completed the e-survey. In the 12 months prior to the survey, 29% of 76 units reported at least one symptomatic case of fracture associated with metabolic bone disease of prematurity, and 18% of 76 units reported at least one case of craniofacial deformity. Most centres followed local guidelines for diagnosis (77% of 73 units) and treatment (63% of 72 units). Alkaline phosphatase was the blood marker most used for treatment indication (81% of 72 units), and phosphate supplementation was the treatment most used (82% of 71 units). CONCLUSION: Metabolic bone disease of prematurity remains clinically relevant. Wide variations in diagnostic procedures and management strategies were observed in European neonatal units. Evidence-based consensus guidelines appear urgently needed to reduce the number of symptomatic cases.

Bone turnover prediction in patients with chronic kidney disease (CKD) undergoing hemodialysis using shortened dynamic 18F-NaF PET/CT Ki-Patlak.

This study investigated whether Ki-Patlak derived from a shortened scan time for dynamic 18F-NaF PET/CT in chronic kidney disease (CKD) patients undergoing hemodialysis can provide predictive accuracy comparable to that obtained from a longer scan. Twenty-seven patients on chronic hemodialysis, involving a total of 42 scans between December 2021 and August 2023 were recruited. Dynamic 18F-NaF PET/CT scans, lasting 60-90 min, were immediately acquired post-injection, covering the mid-twelfth thoracic vertebra to the pelvis region. Ki-Patlak analysis was performed on bone time-activity curves at 15, 30, 45, 60, and 90 min in the lumbar spine (L1-L4) and both anterior iliac crests. Spearman's rank correlation (rs) and interclass correlation coefficient were used to assess the correlation and agreement of Ki-Patlak between shortened and standard scan times. Bone-specific alkaline phosphatase (BsAP) and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) were tested for their correlation with individual Ki-Patlak. Strong correlations and good agreement were observed between Ki-Patlak values from shortened 30-min scans and longer 60-90-min scans in both lumbar spine (rs = 0.858, p < 0.001) and anterior iliac crest regions (rs = 0.850, p < 0.001). The correlation between BsAP and Ki-Patlak in the anterior iliac crests was weak and statistically insignificant. This finding suggests that a proposed shortened dynamic 18F-NaF PET/CT scan is effective in assessing bone metabolic flux in CKD patients undergoing hemodialysis, offering a non-invasive alternative approach for bone turnover prediction.

Vitamin D and bone health: What vitamin D can and cannot do.

Historically vitamin D deficiency had devastating consequences for children causing rickets resulting in severe bone deformities often leading to death. The mystery of the cause of rickets finally came to light when it was observed that cod liver oil and sunlight could prevent and cure rickets. The first vitamin D to be discovered was vitamin D2 from ergosterol in ultraviolet irradiated yeast. Vitamin D3 was discovered from UV exposure to the skin. Investigations revealed the two major functions of vitamin D were to increase intestinal calcium and phosphate absorption and mobilize calcium from the skeleton to maintain calcium and phosphorus homeostasis. Later studies demonstrated that vitamin D does not have an active role in bone mineralization. Vitamin D deficiency results in secondary hyperparathyroidism increasing bone resorption. As a result, this decreases bone mineral content and compromises the architectural integrity increasing risk for fracture. Vitamin D deficiency has also been shown to enhance aging of the bone causing cracks and enhancing bone fractures. Vitamin D deficiency also causes osteomalacia. Therefore, vitamin D sufficiency is extremely important to maximize bone health throughout life. It helps to prevent bone loss, but it cannot restore bone loss due to increased bone resorption that can occur under a variety of circumstances including menopause. The Endocrine Society Guidelines recommends for all ages that adequate vitamin D obtained from the sun, foods and supplements is necessary in order to maintain a circulating concentration of 25-hydroxyvitamin D of at least 30 ng/mL for maximum bone health.

Assessment of regional and total skeletal metabolism using 18F-NaF PET/CT in patients with chronic kidney disease.

OBJECTIVE: The study aims to assess regional and total bone metabolic activity in patients with chronic kidney disease using Na[18F]F PET and correlation between semi-quantitative indices and blood parameters. METHODS: Seventy-two subjects (mean age 61.8 ± 13.8 years) were included. Of these 24/72 patients had end-stage renal disease (ESRD) (GFR < 15 mL/min/1.73 m2), 38/72 had chronic kidney disease (CKD) (GFR between 60 and 15 mL/min/1.73 m2), and 10/72 were controls with normal renal function. All subjects underwent Na[18F]F PET-CT with a dose activity of 0.06 mCi/Kg. Regional and total skeletal metabolism were assessed with mean SUVs in a skeletal volume of interest (VOI), bone to soft tissue index (B/S), global SUV mean (GSUV mean) of the whole bone, and uptake in the femoral neck. RESULTS: Statistically significant differences were observed in a number of 18F-NaF metrics like femoral neck metabolism in CKD and ERSD groups in comparison to control in right (P = 0.003) and left femur (P = 0.006), bone to soft tissue index in the femur (P = 0.016) and GSUV5 (P = 0.006). There is also a significant difference in SUV mean in lumbar vertebrae (L1-L4) among CKD, ESRD, and controls. There was a moderate correlation between 18F-NaF PET scan uptake and blood parameters such as ALP and PTH. Na[18F]F uptake parameters were significantly different in low versus high bone turnover state. CONCLUSIONS: The assessment of total skeleton and regional metabolism and bone turnover in CKD patients is feasible with Na[18F]F PET. Na[18F]F can help to detect early changes in bone metabolism and assess the progression of bone disease in this complex condition. Quantification with Na[18F]F PET might provide better assessment of the bone turnover. The difference in Na[18F]F uptake in CKD compared to controls is likely related to a change in bone turnover which, however, requires further validation.

Blood fibroblast growth factor 23 concentration in cats with and without chronic kidney disease: a scoping review.

OBJECTIVES: This study undertook a scoping review of research on blood fibroblast growth factor 23 (FGF-23) concentrations in healthy non-azotemic cats and cats with chronic kidney disease (CKD) to describe the volume and nature of existing literature, to determine whether published studies provide adequate evidence to support the use of FGF-23 as a biomarker in clinical practice and to identify any existing gaps in knowledge. METHODS: PRISMA Extension for Scoping Reviews guidelines were used to design and perform the scoping review. Online databases were used to identify observational and clinical studies of blood FGF-23 concentrations in healthy cats and cats with CKD published before December 2022. Study and population characteristics and descriptive data on FGF-23 concentrations were extracted. RESULTS: A total of 205 publications were reviewed; 17 were retained for inclusion. Most studies were retrospective. Most studies included cats with International Renal Interest Society stage 2-4 CKD, with some variation. Key concepts explored in the literature include FGF-23 concentrations by CKD stage, effect of dietary phosphate restriction on FGF-23 concentrations, relationship between FGF-23 concentrations and blood phosphorus, calcium and magnesium concentrations, and FGF-23 concentrations in cats with progressive CKD. FGF-23 concentrations tended to be higher in cats with CKD compared with healthy cats, with an overlap between healthy and CKD populations, and there was significant variation within stages of CKD. CONCLUSIONS AND RELEVANCE: FGF-23 is a biomarker of interest for the management and monitoring of phosphate overload in cats. Studies support several potential clinical applications for measuring FGF-23 concentration in practice; however, evidence is limited. Research on FGF-23 in cats with CKD would benefit from longitudinal, prospective studies that standardize CKD diagnosis and categorize cats by stage using current guidelines. Studies should include cats with early-stage, non-azotemic CKD and use commercially available assays so such results are comparable across studies.

Diagnosis and therapeutic decisions of osteoporosis in chronic kidney disease.

A 63-yr-old woman with end-stage CKD secondary to glomerulonephritis, on hemodialysis therapy, presented with scoliosis, back pain, and progressive loss of physical function for which corrective surgery was planned. Optimization of bone health was requested by the surgeon as a DXA scan had revealed osteoporosis at spine, hip, and forearm. Due to previous subtotal parathyroidectomy and normal parathyroid hormone and bone-specific alkaline phosphatase levels, a low bone turnover state was suspected. An iliac bone biopsy was performed and revealed low bone turnover, a mineralization defect, and severe osteoporosis. The patient was treated with calcium and intensified vitamin D supplementation, followed by a 2-yr course of teriparatide. Monitoring of bone turnover markers indicated a bone anabolic response to therapy, and a repeat DXA showed increases in BMD at spine and hip. A repeat biopsy at end of treatment showed normal bone turnover and mineralization. This case demonstrates the complicated bone health of patients with advanced CKD. As there are no randomized trials for fracture pretention in patients with CKD, care must be individualized and is often based on expert opinion. The use of bone biopsy is safe and informative in guiding therapy.

Skeletal consequences of preterm birth in pigs as a model for preterm infants.

Preterm birth affects about 10% of all live births with many resultant health challenges, including metabolic bone disease of prematurity (MBDP), which is characterized by elevated alkaline phosphatase, suppressed phosphate, and deficient skeletal development. Because of the lack of an animal model, very little is known about bone structure, strength, and quality after preterm birth. This study investigated the utility of a pig model to replicate clinical features of preterm birth, including MBDP, and sought to determine if early postnatal administration of IGF-1 was an effective treatment. Preterm pigs, born by caesarean section at 90% gestation, were reared in intensive care facilities (respiratory, thermoregulatory, and nutritional support) and compared with sow-reared term pigs born vaginally. Preterm pigs were systemically treated with vehicle or IGF-1 (recombinant human IGF-1/BP-3, 2.25 mg/kg/d). Tissues were collected at postnatal days 1, 5, and 19 (the normal weaning period in pigs). Most bone-related outcomes were affected by preterm birth throughout the study period, whereas IGF-1 supplementation had almost no effect. By day 19, alkaline phosphatase was elevated, phosphate and calcium were reduced, and the bone resorption marker C-terminal crosslinks of type I collagen was elevated in preterm pigs compared to term pigs. Preterm pigs also had decrements in femoral cortical cross-sectional properties, consistent with reduced whole-bone strength. Thus, the preterm pig model replicates many features of preterm bone development in infants, including features of MBDP, and allows for direct interrogation of skeletal tissues, enhancing the field's ability to examine underlying mechanisms.

Premature birth interrupts a critical period of skeletal development as the majority of fetal bone mineral accumulation occurs during the last gestational trimester, leaving preterm infants at increased risk for low bone mineral density and fractures. Although there are some data on growth in bone mass in preterm infants, very little is known about bone structural properties, quality, and strength during development after preterm birth. In this study, we sought to evaluate the pig as a model for postnatal skeletal development after premature birth. Preterm pigs born after approximately 90% of the full gestation period were compared to full-term control pigs through day 19 of life. Levels of 2 blood markers used to diagnose osteoporosis of prematurity were replicated in the pig model. Bone properties related to strength were reduced even when accounting for their smaller body size, possibly suggesting elevated fracture risk in preterm infants. Based on the similarities between the preterm pig model and preterm human infants, the pig model may prove to be useful to study factors and interventions affecting postnatal bone development after preterm birth.

Effect of early preventive supplementation with calcium and phosphorus on metabolic bone disease in premature infants.

OBJECTIVE: The objective was to study the effect of early preventive calcium and phosphorus supplementation on metabolic bone disease in preterm infants. METHODS: A retrospective analysis of 234 preterm infants with a gestational age < 32 weeks or birth weight < 1500 g who were hospitalized in the Neonatology Department of the Second Hospital of Shandong University from 01.2018 to 12.2020 was conducted. One hundred thirty-two premature infants hospitalized from 01.2018 to 06.2019 did not receive prophylactic calcium and phosphorus supplementation in the early postnatal period. These infants received calcium or phosphorus supplementation at the time of hypocalcaemia or hypophosphatemia diagnosis. One hundred two premature infants hospitalized from 07.2019 to 12.2020 received early preventive calcium and phosphorus supplementation after birth. The levels of serum calcium and phosphorus, alkaline phosphatase, 25-hydroxyvitamin D, calcitonin, and parathyroid hormone at different time points and growth indicators at six months of age were compared between the two groups of infants. The number of cases of metabolic bone disease and fracture between the two groups was compared. RESULTS: 1) A total of 12 infants (5.13%) among the 234 preterm infants were diagnosed with metabolic bone disease, including 2 (1.96%) in the prophylactic supplementation group and 10 (7.58%) in the nonprophylactic supplementation group. Fractures occurred in 3 premature infants (25.0%) with metabolic bone disease, all of whom were in the group that did not receive prophylactic supplementation. 2) There was no significant difference in serum calcium and calcitonin levels between the two groups. The levels of serum phosphorus and 25 hydroxyvitamin D in the prophylactic supplementation group were higher than those in the nonprophylactic supplementation group (P < 0.05). In comparison, alkaline phosphatase and parathyroid hormone levels were lower in the prophylactic supplementation group than in the nonprophylactic supplementation group (P < 0.05). Preterm infants in the prophylactic supplementation group had higher weight, length, head circumference, and bone density values than those in the nonprophylactic supplementation group (P < 0.05). CONCLUSION: Preventive supplementation with calcium and phosphorus after birth can effectively improve calcium and phosphorus metabolism, and reduce the incidence of metabolic bone disease and fractures in premature infants. This can be further publicized and used clinically.

Characteristics of femoral neck fractures in osteogenesis imperfecta: Series of four-teen consecutive hips in twelve patients.

INTRODUCTION: While long bone fractures are commonly seen in individuals with Osteogenesis Imperfecta (OI), femoral neck fractures (FNF) are exceedingly rare. There is a lack of comprehensive data regarding the etiology of FNFs, their characteristics, and the treatment protocols. Our aim was to determine the characteristics of femoral neck fractures in children with OI. MATERIALS AND METHODS: This study was conducted as retrospective series covering period of January 2011-December 2022. Total of 14 femoral neck fractures in 12 patients were included into final analysis. Age, gender, fracture location, ambulation level, injury mechanism, Sillence type, pre-fracture collo-diaphyseal angle, presence of previous implants and applied treatments were noted. RESULTS: The mean age was 9.3 (range: 3-16), 8 out of 12 patients were males. Sillence type 3 OI was most common (50 %) type. Among 12 patients, 2 (16.6 %) were restricted ambulatory while 5 (41.6 %) were non-ambulatory. Seven patients had prior femoral implants. Six fractures were managed non-operatively, while others underwent surgery, with cannulated screws (42.8 %) or plate osteosynthesis (7.1 %). All eight cases (100 %) with minor trauma or unknown origin were Sillence type 3-4, displaying varus deformity. FNFs that occured in mobile patients required higher-energy traumas. CONCLUSION: Femoral neck fractures in OI showed differing trauma mechanisms in ambulatory vs. non-ambulatory patients. Non-surgical treatment may be considered with in patients with high-risk anesthesia concerns, requiring higher level clinical studies.

Pyridoxine challenge reflects pediatric hypophosphatasia severity and thereby examines tissue-nonspecific alkaline phosphatase's role in vitamin B6 metabolism.

Alkaline phosphatase (ALP) is detected in most human tissues. However, ALP activity is routinely assayed using high concentrations of artificial colorimetric substrates in phosphate-free laboratory buffers at lethal pH. Hypophosphatasia (HPP) is the inborn-error-of-metabolism caused by loss-of-function mutation(s) of the ALPL gene that encodes the ALP isoenzyme expressed in bone, liver, kidney, and elsewhere and is therefore designated "tissue-nonspecific" ALP (TNSALP). Consequently, HPP harbors clues concerning the biological function of this phosphohydrolase that is anchored onto the surface of cells. The biochemical signature of HPP features low serum ALP activity (hypophosphatasemia) together with elevated plasma levels of three natural substrates of TNSALP: i) phosphoethanolamine (PEA), a component of the linkage apparatus that binds ALPs and other proteins to the plasma membrane surface; ii) inorganic pyrophosphate (PPi), an inhibitor of bone and tooth mineralization; and iii) pyridoxal 5'-phosphate (PLP), the principal circulating vitameric form of vitamin B6 (B6). Autosomal dominant and autosomal recessive inheritance involving several hundred ALPL mutations underlies the remarkably broad-ranging expressivity of HPP featuring tooth loss often with muscle weakness and rickets or osteomalacia. Thus, HPP associates the "bone" isoform of TNSALP with biomineralization, whereas the physiological role of the "liver", "kidney", and other isoforms of TNSALP remains uncertain. Herein, to examine HPP's broad-ranging severity and the function of TNSALP, we administered an oral challenge of pyridoxine (PN) hydrochloride to 116 children with HPP. We assayed both pre- and post-challenge serum ALP activity and plasma levels of PLP, the B6 degradation product pyridoxic acid (PA), and the B6 vitamer pyridoxal (PL) that can enter cells. Responses were validated by PN challenge of 14 healthy adults and 19 children with metabolic bone diseases other than HPP. HPP severity was assessed using our HPP clinical nosology and patient height Z-scores. PN challenge of all study groups did not alter serum ALP activity in our clinical laboratory. In HPP, both the post-challenge PLP level and the PLP increment correlated (Ps < 0.0001) with the clinical nosology and height Z-scores (Rs = +0.6009 and + 0.4886, and Rs = -0.4846 and - 0.5002, respectively). In contrast, the plasma levels and increments of PA and PL from the PN challenge became less pronounced with HPP severity. We discuss how our findings suggest extraskeletal TNSALP primarily conditioned the PN challenge responses, and explain why they caution against overzealous B6 supplementation of HPP.

Osteoporosis and cement usage in total hip arthroplasty.

PURPOSE: Cement usage in total hip arthroplasty (THA) is increasingly common. However, osteoporosis-related fracture risk in cemented vs uncemented THA patients is poorly characterized. We aim to analyze the usage of metabolic bone care and osteoporosis fracture risk in cemented vs uncemented THA patients using FRAX and radiographic bone measurements. METHODS: Chart review on 250 THA patients was performed retrospectively. Demographics, FRAX scores, hip radiograph measurements, osteoporosis diagnosis, treatment and screening were compared between cemented and uncemented THA patients. Logistic regression model was used to analyze factors influencing cement usage. RESULTS: Cemented THA patients have significantly higher osteoporosis-related fracture risk as measured by FRAX major (20% vs 13%) and FRAX hip (8% vs 5%). There is no significant difference in osteoporosis treatment, vitamin D / calcium supplementation, or metabolic bone disease screening based on patients' cement status. Female sex and rheumatoid arthritis status significantly predict cement usage, but FRAX scores do not predict cement usage. Additionally, 50% (10/20) of patients with Dorr C classification were uncemented. CONCLUSION: Although some patients undergoing THA with high osteoporosis-related fracture risk were identified and cemented, some risk factors including poor proximal femur shape (by Dorr classification) and poor bone quality (as measured by FRAX score) were potentially overlooked. Cemented patients had an increased risk for fractures but did not receive appropriately increased osteoporosis screening or treatment. LEVEL OF EVIDENCE: III.

Neurodevelopment Outcomes in Very-Low-Birth-Weight Infants with Metabolic Bone Disease at 2 Years of Age.

Metabolic bone disease (MBD) predominantly affects preterm infants, particularly very-low-birth-weight (VLBW) infants weighing <1500 g. However, there are limited reports on MBD and neurodevelopmental outcomes. This study aimed to analyze the risk factors for MBD and understand its impact on neurodevelopmental outcomes at 2 years of corrected age. Overall, 749 VLBW infants weighing <1350 g at birth were enrolled. Exclusion criteria were major congenital abnormalities, chromosomal abnormalities, and loss of follow-up on the Bayley Scales of Infant Development, Third Edition (BSID-III) test at 24 months of corrected age. Infants were retrospectively assessed by a trained case manager using the BSID-III test at 6, 12, and 24 months old. Infants were categorized as with or without MBD according to radiographic signs. Of those enrolled, 97 VLBW infants were diagnosed with MBD, compared to 362 VLBW infants without MBD. The proportion of infants that completed three follow-ups was 86%. At the assessment at 2 years of age, infants with MBD had lower and more significant differences in motor, language, and cognitive composites. MBD is associated with poor neurodevelopmental outcomes in cognitive, motor, and language composites for VLBW infants at 24 months of corrected age.

Non-neoplastic bone, joint, and soft tissue pathology: What every pathologist should know.

The diagnosis of bone and soft tissue tumors is a skill which requires experience across multiple disciplines while their incidence is small. By contrast, the numbers of patients with non-tumorous diseases of bones, soft tissues, and joints dwarfs primary tumors by several orders of magnitude. The ability to successfully diagnose non-neoplastic diseases requires a knowledge of bone development, structure, remodeling, imaging, and tissue processing. This review summarizes the alterations of bones, joints, and to a lesser extent soft tissues that are encountered in the practice of everyday surgical pathology.

Continuous versus intermittent bolus infusion of calcium in preterm infants receiving total parenteral nutrition: a randomized blind clinical trial.

BACKGROUND: Premature neonates need adequate nutritional support to provide sufficient essential nutrients for optimal growth. Calcium (Ca) is one of the important nutrients in parental nutrition support of premature infants. This study aimed to compare the effect of continuous and intermittent bolus infusion of Ca on the incidence of metabolic bone disease (MBD) in preterm infants. METHODS: This randomized double-blind clinical trial was conducted on ninety preterm infants in the NICU of Al-Zahra Hospital in Tabriz, Iran. The preterm infants were randomly allocated to either a continuous infusion group (received 4-5 ml/kg/day of Ca gluconate 10% by PN solution in a 24-h period) or an intermittent bolus administration group (received 1-2 ml/kg/day Ca gluconate 10% three to four times per day). Serial serum levels of Ca, phosphorous, alkaline phosphatase (ALP), vitamin D and parathyroid hormone (PTH) were assessed on the 7th day, 30th day and 45th day of life. RESULTS: A total of 78 infants completed the study. The serum ALP level on the 45th day after birth was 753.28 ± 304.59 IU/L and 988.2 ± 341.3 IU/L in the continuous infusion and intermittent bolus administration groups, respectively (P < 0.05). MBD in preterm infants with ALP levels above 900 IU/L on the 45th day of life was significantly lower in the continuous infusion group than in the intermittent bolus administration group (p < 0.05). The mean serum levels of calcium, phosphorus, vitamin D and PTH in 45-day-old infants were not significantly different between the two groups. CONCLUSION: The MBD in preterm infants who received continuous infusion of Ca was lower than that in preterm infants who received intermittent bolus administration of Ca. TRIAL REGISTRATION: The Iranian Registry of Clinical Trials ( http://www.irct.ir ) with the identification No. IRCT20210913052466N1.