Normal Serum 25-hydroxyvitamin Research Articles

Vitamin D and pediatric bone health: Important information and considerations for the pediatric orthopaedic surgeon

Vitamin D is an essential fat-soluble vitamin produced in the skin during sun exposure. It plays a considerable role in musculoskeletal health and is largely responsible for the regulation of calcium and phosphate metabolism to maintain a healthy, mineralized skeleton. Optimizing bone mineral density in childhood and adolescence is essential to the foundation of skeletal health; however, the literature lacks consensus on values for normal, deficient, and insufficient serum 25-hydroxyvitamin D levels making supplementation and treatment somewhat challenging.The pediatric orthopaedic surgeon is important to optimizing bone health, particularly in the context of bony pathology/injury. Up to 60% of boys and 40% of girls sustain a fracture in childhood. On top of this baseline incidence, children with low vitamin D levels have been noted to be subject to a higher incidence of fractures from normal activities. While the prevalence of vitamin D deficiency in children in the general population has been determined to be 9%, the prevalence of vitamin D deficiency in the pediatric fracture population can be as high as 75% and 61% of the pediatric population has been determined to have vitamin D insufficiency. The pediatric orthopedist also often is the first to diagnose nutritional rickets as these patients can present solely for complaints of limb deformity. Knowledge of appropriate evaluation, vitamin D supplementation, and indications for pediatric endocrinology referral is vital for the treatment of these patients.In the pediatric population, there is a lack of consensus regarding risk factors that warrant screening for vitamin D deficiency, determining insufficient thresholds, and identifying optimal supplementation recommendations and treatment dosages. More research is needed to clarify the ideal amounts of vitamin D necessary through critical growth periods to prevent rickets and to mitigate fracture risk. Regardless, pediatric Orthopaedic surgeons should promote supplementation to all children and treat diagnosed vitamin D deficiency. Key Concepts(1)Vitamin D plays a vital role in musculoskeletal health and optimizing vitamin D levels in childhood and adolescence is crucial to proper bone development.(2)Vitamin D deficiency and insufficiency in the general population is common; 9% of the pediatric population, representing 7.6 million US children and adolescents, are vitamin D deficient and 61%, representing 50.8 million US children and adolescents, are vitamin D insufficient. The prevalence of vitamin D deficiency in the pediatric fracture population can be as high as 75%.(3)Vitamin D deficiency can lead to nutritional rickets which is the most frequent cause of pediatric bone disease in the world, is entirely preventable, and is characterized by deficient mineralization and subsequent architectural disruption of the physis.(4)Vitamin D supplementation is widely recommended and believed to be beneficial, but there are inconsistent guidelines regarding target levels for optimal vitamin D status.

Correlation between obesity and serum 25-hydroxyvitamin D levels in patients with type 2 diabetes

[Objective] The paper analyzes the correlation of vitamin D level with obesity degree and serum 25-hydroxyvitamin D level in patients with type 2 diabetes mellitus (T2DM) through clinical case studies, which can provide clinical guidance for obese T2DM patients' weight control to lower their risk of developing metabolic illnesses. [Methods] A total of 249 patients with T2DM were chosen from among those hospitalized at Lanzhou University's First Hospital between April and September of 2023. The serum 25-hydroxyvitamin D level, body fat rate, fasting blood glucose, and fasting insulin of the subjects were detected, and 198 T2DM patients with low serum 25-hydroxyvitamin D levels were selected as the observation group. 51 T2DM patients with normal serum 25-hydroxyvitamin D levels were selected as the control group, and the correlation between type 2 diabetes mellitus and vitamin D levels and obesity was analyzed. [Results] Obesity and serum vitamin D insufficiency are associated with type 2 diabetes. Both vitamin D deficiency and obesity eventually lead to T2D, endocrine disorders, and other common diseases. [Conclusions] Low plasma 25-hydroxyvitamin D (25[OH]D) concentration and high BMI are correlated with an increased risk of diabetes.

Neonate with Respiratory Distress, Bilateral Microtia, Hypocalcemia, and Lymphopenia.

Neonate with Respiratory Distress, Bilateral Microtia, Hypocalcemia, and Lymphopenia.

Oral and Topical Vitamin D, Sunshine, and UVB Phototherapy Safely Control Psoriasis in Patients with Normal Pretreatment Serum 25-Hydroxyvitamin D Concentrations: A Literature Review and Discussion of Health Implications.

Vitamin D, sunshine and UVB phototherapy were first reported in the early 1900s to control psoriasis, cure rickets and cure tuberculosis (TB). Vitamin D also controlled asthma and rheumatoid arthritis with intakes ranging from 60,000 to 600,000 International Units (IU)/day. In the 1980s, interest in treating psoriasis with vitamin D rekindled. Since 1985 four different oral forms of vitamin D (D2, D3, 1-hydroxyvitaminD3 (1(OH)D3) and 1,25-dihydroxyvitaminD3 (calcitriol)) and several topical formulations have been reported safe and effective treatments for psoriasis—as has UVB phototherapy and sunshine. In this review we show that many pre-treatment serum 25(OH)D concentrations fall within the current range of normal, while many post-treatment concentrations fall outside the upper limit of this normal (100 ng/mL). Yet, psoriasis patients showed significant clinical improvement without complications using these treatments. Current estimates of vitamin D sufficiency appear to underestimate serum 25(OH)D concentrations required for optimal health in psoriasis patients, while concentrations associated with adverse events appear to be much higher than current estimates of safe serum 25(OH)D concentrations. Based on these observations, the therapeutic index for vitamin D needs to be reexamined in the treatment of psoriasis and other diseases strongly linked to vitamin D deficiency, including COVID-19 infections, which may also improve safely with sufficient vitamin D intake or UVB exposure.

SAT-341 Hyperparathyroid Crisis Precipitated by Rapid Correction of Symptomatic Hypercalcemia in an Occult Ectopic Parathyroid Adenoma

Background: Parathyroid adenomas (PA) are typically benign, slow-growing tumors causing gradual increase in parathyroid hormone (PTH) and serum calcium (s.Ca) levels. Hyperparathyroid crisis is a rare and potentially fatal syndrome, which occurs due to rapid elevation of PTH and s.Ca levels (s.Ca >15mg/dL). This can potentiate severe metabolic derangements, manifesting as altered mental status (AMS), renal insufficiency and cardiac arrhythmias. We present a case of hyperparathyroid crisis in the setting of an occult ectopic parathyroid adenoma.Case: 75 year old female with a medical history of osteoporosis, hypertension and Parkinson’s disease, presented to our hospital with AMS and one week history of diarrhea. She was recently hospitalized for pneumonia and treated with antibiotics. Biochemical analysis revealed corrected s.Ca 15.4mg/dL (8.2- 9.6mg/dL; 7 days prior s.Ca was 9.7mg/dL), renal insufficiency (Cr 2.26mg/dL; baseline 1.2) with normal serum phosphorus, magnesium, 25-hydroxyvitamin D and alkaline phosphatase. PTH was found to be elevated at 75pg/mL (15-65pg/mL). She was treated with aggressive intravenous hydration and calcitonin 200mg BID for 3 days. Her s.Ca appropriately trended down. However, her PTH level continued to rise: 319pg/mL 12 hours later, 591pg/mL on day 2 and peaked to 1,242pg/mL on day 3. CT angiography neck showed an incidental finding of a heterogeneous, possibly necrotic, soft tissue nodule in the left paraesophageal region. Additional work-up with technetium 99 Sestamibi scan revealed persistent activity in the upper tracheoesophageal groove consistent with an ectopic PA. She underwent parathyroid exploration with excision of an enlarged ectopic left superior parathyroid adenoma, confirmed on histopathological analysis. The remaining parathyroid glands were normal. PTH declined to 34pg/mL postoperatively. Her mental status improved significantly returning to baseline within a few days with normal PTH and s.Ca levels.Discussion: Secretion of PTH is mediated by s.Ca via the calcium sensing receptors (CaSR). Studies have shown that patients with PA have decreased expression of the CaSR leading to an autonomous rise in PTH secretion and a higher PTH-calcium set point. In our case, the patient initially presented with a mildly elevated PTH level and symptomatic hypercalcemia. The rapid correction of s.Ca levels precipitated a remarkable rise in PTH levels. We postulate that this was caused by a possible upregulation mechanism in calcium sensing by adenomatous parathyroid tissue that is responsive to acute lowering of s.Ca levels, triggering a hyperparathyroid crisis.Reference: (1) Corbetta S., et al. Calcium-sensing receptor expression and signaling in human parathyroid adenomas and primary hyperplasia. Clinical Endocrinology. 2000; 52(3):339-48.

SUN-LB19 Novel Homozygous Mutation in BMP1 Causing Osteogenesis Imperfecta

Background: Osteogenesis imperfecta (OI) is characterized by bone fragility and increased fracture susceptibility. Most mutations occur in COL1A1 and COL1A2 genes. Rarely, mutations in BMP1 have been reported in association with OI type XIII. Disease severity is generally more severe when the mutation affects both gene products encoded by BMP1 that serve as procollagenases: bone morphogenic protein 1 and mammalian tolloid (mTLD) [1]. Clinical Case: A 7-year-old Hispanic boy, with speech and gross motor delays, sustained five bilateral tibial fractures with minimal trauma since age 2.5 years. At age 6 years, he developed severe back pain after a minor fall. Diffuse spinal osteopenia and multiple vertebral compression fractures (VCF) at T9, L1, L3 were identified radiographically, with progressive vertebral height loss in the ensuing 9 months. Fatigue was reported after walking >10 min, with difficulty running and climbing stairs. There was no family history of musculoskeletal disorders.Stature was consistently between 10-15th% for age. Subtle facial dysmorphism included micrognathia and small chin, with patchy blue-gray sclerae, and normal dentition. The lumbar spine was tender to percussion. Gait was slow and antalgic with external rotation of the right hip.Laboratory evaluation revealed normal serum calcium, iPTH, magnesium, phosphate, 25-hydroxyvitamin D and alkaline phosphatase for age. P1NP was slightly high (193 µg/L, 30-110 µg/L) and CTX was slightly low (554 pg/mL, n: 574-1849 pg/mL), the latter being atypical for OI. Total hip BMD (adjusted for height Z-score) was normal (Z-score = 1.76) and adjusted femoral neck BMD was high (Z-score = 2.67). VCFs precluded assessment of lumbar spine BMD. Genomic analysis revealed a homozygous missense mutation in exon 4 of BMP1 resulting in an amino acid substitution (c. C505T; p.Arg169Cys) in both the bone morphogenetic protein 1 and mTLD gene products of BMP1. The mutation is predicted to be damaging to both proteins, and associated with this rare form of OI. Conclusion: We report a novel homozygous mutation in BMP1 identified in a child with autosomal recessive OI. Unlike most forms of OI, patients with type XIII often have normal or increased BMD [1], making a correlation between BMD and fracture risk difficult. While bisphosphonates (BP) may help reduce recurrent fractures and provide symptomatic relief, the broad phenotypic spectrum and concern for further increasing BMD complicate management. A high resolution peripheral quantitative CT scan to assess bone microarchitecture and quality may aid in the decision of BP therapy. As evidence is limited on the effectiveness of BP in this rare form of OI, it is important to consider each case individually.1.Sangsin, A., et al., Two novel compound heterozygous BMP1 mutations in a patient with osteogenesis imperfecta: a case report. BMC Med Genet, 2017. 18(1): p. 25.

Factors related to muscle strength in postmenopausal women aged younger than 65 years with normal vitamin D status

Objective: The study aimed to determine the impact of age, age at menopause, body mass index (BMI), and lumbar and hip bone mineral density (BMD) on muscle strength in young postmenopausal women with normal vitamin D levels.Methods: This was a cross-sectional study performed in 392 postmenopausal women aged <65 years with normal serum 25-hydroxyvitamin D levels (≥30 ng/ml) and no physical disabilities. The following variables were recorded: age, age at menopause, BMI, BMD (measured by dual-energy X-ray absorptiometry [DXA] scanning and expressed as lumbar and hip T-scores), and dominant hand grip strength (measured with a digital dynamometer). Results are reported as mean ± standard deviation or odds ratio (OR) and 95% confidence interval (CI) as appropriate.Results: The mean age of the whole sample was 57.30 ± 3.69 years with a mean age at menopause of 50.46 ± 2.16 years and a mean BMI of 24.93 ± 3.78. Mean DXA results were lumbar T-score of −1.16 ± 1.18 and hip T-score of −0.98 ± 0.93. The mean dominant hand grip force was 24.10 kg. A total of 12.2% (48/392) of women were diagnosed with dynapenia using a cut-off value of <20 kg. A weak but significant inverse correlation was found between grip strength in the dominant hand and age (r = −0.131, p = 0.009). Multivariable logistic regression analysis determined that earlier age at menopause (50 years or younger) was significantly associated with a higher risk of dynapenia (OR 2.741, 95% CI 1.23–6.11, p = 0.014). No other significant association was found with the other variables.Conclusions: A total of 12.2% of the studied young postmenopausal women with normal vitamin D status had dynapenia. There was a weak inverse correlation between grip strength and age, and earlier age at menopause was associated with an increased dynapenia risk.

A Retrospective Study Evaluating the Association of Gastric Intestinal Metaplasia and Serum Vitamin D Levels in an Urban Medical Center

Introduction: Recent studies suggest that there is an association between gastric adenocarcinoma and low serum vitamin D levels. However, to date, there are no studies in the literature that have investigated the relationship between the premalignant stages of gastric adenocarcinoma such as intestinal metaplasia and low serum vitamin D levels. Methods: A retrospective, randomized and matched case-control study was conducted with cases defined as subjects who had intestinal metaplasia identified by gastric biopsy and the controls classified as subjects who did not have intestinal metaplasia detected by biopsy and were therefore healthy. All subjects who were included were older than 18 years old, had underwent EGD and had a documented serum 25-hydroxyvitamin D level prior to EGD without repletion. Subjects that were excluded included those who were younger than 18 years old, did not undergo EGD, subjects who did not have a documented Vitamin D level prior to EGD, or if the patient had prior gastrectomy, gastric ulcers, adenomatous polyps, intestinal metaplasia of the esophagus or malignancy including gastric cancer. The cases and control subjects were matched according to age, gender, ethnicity, Body Mass Index (BMI), and H. Pylori infection. A normal serum 25-hydroxyvitamin D level was defined as 30-100 ng/dL. Hypovitamonosis D was divided into two groups based on severity: Vitamin D insufficiency (VDi) and Vitamin D deficiency (VDd). A serum 25-hydroxyvitamin D level that was 20 ng/dL or greater but less than 30 ng/dL was considered VDi in contrast with VDd that was defined as a level less than 20 ng/dL. The mean and standard deviation of the matched patients' age, 25-hydroxyvitamin D level, BMI were calculated. The odds ratio was calculated to assess the association between 25-hydroxyvitamin D levels and Gastric Intestinal Metaplasia with statistical significance defined as a p-value < 0.05. Results: 906 subjects were recruited for this study and 324 subjects met the inclusion criteria. After matching, 168 subjects were included in the final analysis; 84 cases and controls each. The case and control subjects were similar in regards to age, gender, ethnicity, and BMI; most subjects were female (63.1%), Hispanic (77.4%), overweight, and did not have H. Pylori infection (75%). The average serum 25-hydroxyvitamin D level was lower in the Intestinal Metaplasia group (21.88 ng/dL) in comparison with patients who did not have evidence of Intestinal Metaplasia 32.26 ng/dL). Hypovitaminosis D was more common in patients with Intestinal Metaplasia (OR 12.6). Most patients with Intestinal Metaplasia who were found to have hypovitamosis D were more likely to have VDi (OR 78.76) than VDd (OR 34.61). All results had a p-value < 0.01. Conclusion: Although the development of intestinal metaplasia is multifactorial, hypovitaminosis D may contribute as a treatable risk factor.Table: Table. Demographic Information

Hereditary Hypophosphatemic rickets with Hypercalciuria: A case report and review of literature

Hereditary hypophosphatemic rickets with Hypercalciuria (HHRH) is one of the four entities of hereditary hypophosphatemic rickets, characterized by vitamin D refractory rickets, Hyperphosphaturia, Hypercalciuria, hypophosphatemia, elevated serum 1, 25-dihydroxyvitamin D levels, normal serum Calcium, 25-hydroxyvitamin D and PTH levels. Clinically, it is difficult to differentiate the four entities without a genetic test. However, presence of Hypercalciuria by a simple bedside urine examination of spot calcium-creatinine ratio differentiates HHRH from other three entities of hereditary hypophosphatemic rickets. Correction of all the abnormalities, except for renal inorganic phosphate wasting can be achieved by simple prescription of oral phosphate supplementation. It is also the only type of refractory rickets in which Vitamin D supplementation is more hazardous than beneficial. In this study, we review the literature and describe a case of two year old female child who presented with vitamin D refractory rickets at our tertiary level pediatric centre in Cuttack, Odisha, India whose phenotypic characteristics corresponded with HHRH.

Low serum 25-hydroxyvitamin D [25(OH)D] concentrations in type 2 diabetes mellitus patients presenting to a functional medicine clinic

This study explores the relationship of 25-hydroxylvitamin D blood levels in 106 randomly selected patient files with diagnosed type 2 Diabetes Mellitus (t2DM) who enrolled in a functional medicine diabetes reversal program from a chiropractic clinic located in Annapolis, Maryland, USA. Using a conservative recommendation for normal serum 25-hydroxyvitamin D concentration of 32 ng/ml, insufficiency level of 20 - 30 ng/ml, and deficiency level et al. (2011) determined the optimal concentration of serum 25OHD to be 40 ng/ml in order to optimize insulin sensitivity. In our sample 100/ 106 (94%) had vitamin D levels at or below this optimal cut-off level. BMI was negatively correlated with vitamin D; that is, the greater the BMI of the patient the less their vitamin D level. Both obesity and hypovitaminosis D are each mutually exclusive predictors for t2DM. Obesity and vitamin D deficiency may work synergistically to propel an individual into the diseased state of t2DM. As this study demonstrates that the majority of people with t2DM suffer from inadequate amounts of vitamin D, vitamin D testing should be routine for all people at risk for t2DM, prediabetics and those currently suffering with t2DM in order to elevate levels sufficiently to improve insulin sensitivity and improve long-term outcomes.

Effects of Adjunct Low-Dose Vitamin D on Relapsing-Remitting Multiple Sclerosis Progression: Preliminary Findings of a Randomized Placebo-Controlled Trial

The aim of this preliminary study was to evaluate the effect of low-dose oral vitamin D in combination with current disease-modifying therapy on the prevention of progression of relapsing-remitting multiple sclerosis (RRMS). A phase II double-blind placebo-controlled randomized clinical trial conducted between October 2007 and October 2008 included 50 patients with confirmed RRMS aged 25 to 57 years and normal serum 25-hydroxyvitamin D. They were randomly allocated to receive 12 months of treatment with either escalating calcitriol doses up to 0.5 μg/day or placebo combined with disease-modifying therapy. Response to treatment was assessed at eight-week intervals. In both groups, the mean relapse rate decreased significantly (P < 0.001). In the 25 patients treated with placebo, the mean (SD) Expanded Disability Status Scale (EDSS) increased from 1.70 (1.21) at baseline to 1.94 (1.41) at the end of study period (P < 0.01). Average EDSS and relapse rate at the end of trial did not differ between groups. Adding low-dose vitamin D to routine disease-modifying therapy had no significant effect on the EDSS score or relapse rate. A larger phase III multicenter study of vitamin D in RRMS is warranted to more assess the efficacy of this intervention.

Anorexia Nervosa: Russell’s Sign with Concurrent Tetany

A 32-year-old female with a history of binge-purge type anorexia nervosa presented with abdominal pain and weight loss of 8 kg over the preceding 2 weeks. She denied prior diuretic or laxative abuse. Physical examination showed a thin female with a BMI of 14.2 kg/m2. The dorsal aspect of her hands revealed abrasions, callosities, and scarring (Fig. 1). Her hands were contracted in tetany, flexed at the metacarpophalangeal joints, with extension at the interphalangeal joints with the thumb flexed and adducted (Fig. 2). Laboratory studies revealed a serum calcium of 5.3 mg/dl, albumin of 3.0 g/dl, and normal serum 25-hydroxyvitamin D and parathyroid hormone levels. Figure 1 The dorsal aspect of the patient's hands revealed abrasions, callosities, and scarring. Figure 2 The patient's hands were contracted in tetany, flexed at the metacarpophalangeal joints, with extension at the interphalangeal joints with the thumb flexed and adducted. Figure 1 demonstrates Russell’s sign, with abrasions on the dorsum of the hand from contacting the incisors during self-induced vomiting1. This finding is reported in approximately 4% of patients with purging type anorexia nervosa2. Figure 2 shows an obstetrician or accoucheur’s hand, demonstrating the resemblance of tetany to the position one’s hand is held in while performing a vaginal delivery. Tetany of the patient's hands resolved with electrolyte repletion. On endoscopic evaluation, her abdominal pain was found to be secondary to esophagitis, likely from self-induced vomiting.

Fermentation of calcium-fortified soya milk does not appear to enhance acute calcium absorption in osteopenic post-menopausal women

Ageing women may choose to drink soya milk to reduce menopausal symptoms. As fermentation enriches soya milk with isoflavone aglycones, its beneficial qualities may improve. To reduce osteoporotic risk, however, soya milk must be Ca enriched, and it is not known how fermentation affects Ca bioavailability. A randomised crossover pilot study was undertaken to compare the Ca absorption of fortified soya milk with that of fermented and fortified soya milk in twelve Australian osteopenic post-menopausal women. The fortified soya milk was inoculated with Lactobacillus acidophilus American Type Culture Collection (ATCC) 4962 and fermented for 24 h at 37°C. Ca absorption from soya milk samples was measured using a single isotope radiocalcium method. Participants had a mean age of 54·8 (sd 12·3) years, with mean BMI of 26·5 (sd 5·5) kg/m2 and subnormal to normal serum 25-hydroxyvitamin D (mean 62·5 (sd 19·1) nmol/l). Participants consumed 185 kBq of 45Ca in 44 mg of Ca carrier. The mean fractional Ca absorption (α) from soya milk and fermented soya milk was 0·64 (sd 0·23) and 0·71 (sd 0·29), respectively, a difference not of statistical significance (P = 0·122). Although fermentation of soya milk may provide other health benefits, fermentation had little effect on acute Ca absorption.

Survey of vitamin D levels among post‐menopausal Filipino women with osteoporosis

To determine the prevalence of vitamin D inadequacy in a group of Filipino post-menopausal women with osteoporosis. Seventy otherwise healthy post-menopausal Filipino women seen at the University of Santo Tomas Hospital, Section of Rheumatology, were diagnosed with osteoporosis by central dual-energy X-ray absorptiometry (DXA) technique. Levels of serum 25-hydroxyvitamin D were measured using enzyme-linked immunosorbent assay. The mean age of this population was 70 +/- 8 years, with an average of 22 +/- 10 years since menopause, and mean body mass index (BMI) of 22 +/- 1 kg/m(2). Only 30% (21/70) were on calcium plus vitamin D supplementation. Overall serum 25-hydroxyvitamin D levels ranged from 48-128 nmol/L, with a mean of 87 +/- 20.48 nmol/L. Serum 25-hydroxyvitamin D levels were divided as follows: 80-140 nmol/L (adequate), 25-79 nmol/L (inadequate/insufficient), and < 25 nmol/L (deficient). Sixty-four percent (45/70) of subjects had adequate levels while 36% (25/70) had inadequate levels of 25-hydroxyvitamin D. There were no subjects with deficient levels of 25-hydroxyvitamin D. Fischer's exact test did not show a significant association between BMD and 25-hydroxyvitamin D (P = 0.4804). Among this group of women with post-menopausal osteoporosis, only 36% had insufficient levels of 25-hydroxyvitamin D, with none of the subjects having deficient 25-hydroxyvitamin D levels. The majority (64%) had normal serum 25-hydroxyvitamin D levels--comparatively higher than that reported in the literature. These results suggest the possible contribution of factors other than vitamin D deficiency in post-menopausal Filipino women with osteoporosis.

Supplementation with cholecalciferol does not improve glycaemic control in diabetic subjects with normal serum 25-hydroxyvitamin D levels

Studies have suggested that vitamin D may be important for both insulin sensitivity and insulin secretion, and that supplementation with vitamin D may subsequently prevent development of type 2 diabetes. The objective of the current study was to test the hypothesis that supplementation with vitamin D would improve glycaemic control in subjects with type 2 diabetes. Thirty-six subjects with type 2 diabetes, treated with metformin and bed-time insulin, were randomised to supplementation with cholecalciferol (40,000 IU per week) versus placebo for 6 months. Thirty-two subjects participated throughout the entirety of the study. Fasting blood samples were drawn before and at the end of the 6 month study without the previous bed-time insulin injection. The insulin and metformin doses were not changed throughout the study. After 6 months, the fasting glucose, insulin, C-peptide, fructosamine, and HbA(1c) levels were not significantly different from baseline values. In addition, changes in these parameters (values at 6 months minus values at baseline) did not differ between the vitamin D and the placebo group. We were not able to demonstrate that vitamin D supplementation had a significant effect on glucose metabolism in subjects with type 2 diabetes but without vitamin D deficiency. Further studies are needed in larger groups of subjects with type 2 diabetes or impaired glucose tolerance, who also exhibit low serum 25-hydroxyvitamin D levels.

A Prospective Study to Evaluate the Dose of Vitamin D Required to Correct Low 25-Hydroxyvitamin D Levels, Calcium, and Alkaline Phosphatase in Patients at Risk of Developing Antiepileptic Drug-Induced Osteomalacia

The dose of vitamin D3 required to maintain normal serum 25-hydroxyvitamin D levels in epileptic patients was evaluated in a prospective study. Patients were divided into two groups, comprising 14 institutionalized and 18 non-institutionalized subjects; they were taking carbamazepine, phenytoin and phenobarbitone, alone or in combination. The study was divided into a dose titration stage and a further period of assessment on a fixed dose after attainment of normal serum 25-hydroxyvitamin D levels. Seventeen of the 18 non-institutionalized patients achieved normal levels over a period of 12 months; the remaining patient became normal after 15 months. The dose required to achieve normal levels ranged from 400 to 4000 IU/day; three patients required less than 2400 IU vitamin D3, 12 required 2400 IU and three required greater than 2400 IU. All institutionalized patients achieved normal levels over a period of 12 months; six patients required less than 2400 IU, six required 2400 IU and two required greater than 2400 IU vitamin D3. Raised alkaline phosphatase levels occurred in 11 patients, and reverted to normal in six patients during the initial return of 25-hydroxyvitamin D levels to normal. During the second 12 months, when patients were taking a fixed dose of vitamin D3, alkaline phosphatase increased in five patients who had achieved normal levels. During this phase normal 25-hydroxyvitamin D levels were not maintained in five patients. There was a significant seasonal variation of 25-hydroxyvitamin D levels institutionalized patients, being highest in June and lowest in December. Our findings show that while there was a wide range in the dose required to achieve normal serum 25-hydroxyvitamin D levels--between 400 and 4000 IU/day--78 per cent of patients responded to a dose of 2400 IU/day.

Failure of urokinase to resolve Broviac catheter-related bacteremia in children

We have subsequently observed another case of CSF marrow contamination after difficult lumbar puncture in a 4-month-old infant. Clumps of osteoblasts and a bone chip were seen in the cytocentrifuge preparations. REFERENCES 1. Krushall M, Carter S, Ritz L: Contamination of cerebrospinal fluid by vertebral bone-marrow cells during lumbar puncture. N Engl J Med 308:697, 1983. 2. Minton S, Steichen J, Tsang R: Decreased bone mineral content in small-for-gestational age infants compared with appropriate-for-gestational-age infants; normal serum 25hydroxyvitamin D and decreasing parathyroid hormone. J P~:OIA'rR 71:383, 1983. 3. Minton S, Steichcn J, Tsang R: Bone mineral content in term and preterm appropriate-for-gestational-age infants. J PEDIATR 95:1037, 1979.

Decreased Bone Mineral Content in Small-for-Gestational-Age Infants Compared with Appropriate-for-Gestational-Age Infants: Normal Serum 25-Hydroxyvitamin D and Decreasing Parathyroid Hormone

Bone mineral content was determined by photon absorptiometry, adapted for use in neonates, in 23 small-for-gestational-age (SGA) infants of 31 to 42 weeks of gestational age, for 12 weeks. At birth, term SGA infants had lower bone mineral content than term appropriate-for-gestational-age (AGA) infants; postnatal increase in bone mineral content was slow and lagged significantly behind that of term AGA infants. Preterm SGA infants had bone mineral content that was similar to that of preterm AGA infants at birth; postnatal bone mineral content was similar to that of preterm AGA infants, but was decreased compared with the expected intrauterine bone mineral content. Serum 25-hydroxyvitamin D concentrations and parathyroid hormone levels were the same for SGA and AGA infants. Serum 25-hydroxyvitamin D concentrations decreased slightly with postnatal age and remained within normal limits. Serum parathyroid hormone concentrations decreased in both SGA and AGA infants and reached undetectable levels at 10 to 12 weeks of age.

Vitamin D Deficiency and Bone Disease in Patients With Crohn's Disease

The prevalence of vitamin D deficiency in Crohn's disease and the relationship of vitamin D status to metabolic bone disease have not been fully characterized. Serum 25-hydroxyvitamin D was measured in 82 patients with Crohn's disease; 65% of Crohn's disease patients had a low serum 25-hydroxyvitamin D concentration; 25% had deficient levels (less than 10 ng/ml). The lowest 25-hydroxyvitamin D levels were observed in patients with previous ileal resections. Nine patients were studied in detail including transiliac needle bone biopsies; 6 had osteomalacia and 3 osteoporosis. Six patients had repeat bone biopsies 9 to 18 mo after vitamin D treatment. Three patients with osteomalacia and low serum 25-hydroxyvitamin D levels showed histologic improvement after therapy with oral vitamin D restored serum 25-hydroxyvitamin D levels to normal. The adequacy of therapy was assessed accurately by monitoring serum 25-hydroxyvitamin D concentration. Three patients with metabolic bone disease with normal serum 25-hydroxyvitamin D levels at diagnosis did not show histologic improvement after receiving vitamin D.

Hypocalcemia with osteoblastic metastases in a patient with prostate carcinoma: A cause of secondary hyperparathyroidism

A 68 year old man with prostatic carcinoma and extensive painful osteoblastic metastases was discovered to have hypocalcemia (serum calcium 7.1 mg/dl) without evidence of hypoalbuminemia, renal failure or malabsorption. Baseline studies revealed hypocalciuria (24 hour urine calcium <5 mg/day), normal serum phosphate (3.4 mg/dl), low tubular reabsorption of phosphate (68 percent), undetectable serum calcitonin, normal serum 25-hydroxyvitamin D, slightly elevated serum parathyroid hormone level and increased urinary cyclic AMP (8.87 μmol/g creatinine). These studies were compatible with secondary hyperparathyroidism. The intravenous administration of parathyroid extract produced no further change in urinary phosphate but a 25-fold increase in nephrogenous cyclic AMP. Three days administration of intramuscular parathyroid extract slowly and temporarily restored serum calcium to normal levels while increasing urinary cyclic AMP and phosphate. Chemotherapy with cyclophosphamide and 5-fluorouracil rendered the patient free of pain while reducing serum acid and alkaline phosphatase levels and restoring serum total and ionized calcium and urinary cyclic AMP excretion to normal.