Hypovitaminosis D has been identified as a common risk factor for fragility fractures and poor fracture healing. Epidemiological data on vitamin D deficiency have been gathered in various populations, but the association between vertebral fragility fractures and hypovitaminosis D, especially in males, remains unclear. The purpose of this study was to evaluate serum levels of 25-hydroxyvitamin D (25-OH D) in patients presenting with vertebral fragility fractures and to determine whether patients with a vertebral fracture were at greater risk of hypovitaminosis D than a control population. Furthermore, we studied the seasonal variations in the serum vitamin D levels of tested patients in order to clarify the relationship between other known risk factors for osteoporosis and vitamin D levels. We measured the serum 25-OH D levels of 246 patients admitted with vertebral fractures (105 men, 141 female, mean age 69 years, . sd. 8.5), and in 392 orthopaedic patients with back pain and no fractures (219 men, 173 female, mean age 63 years, . sd. 11) to evaluate the prevalence of vitamin D insufficiency. Statistical analysis found a significant difference in vitamin D levels between patients with vertebral fragility fracture and the control group (p = 0.036). In addition, there was a significant main effect of the tested variables: obesity (p < 0.001), nicotine abuse (p = 0.002) and diabetes mellitus (p < 0.001). No statistical difference was found between vitamin D levels and gender (p = 0.34). Vitamin D insufficiency was shown to be a risk factor for vertebral fragility fractures in both men and women. Cite this article: Bone Joint J 2015;97-B:89–93

We measured the plasma 25-hydroxyvitamin D. 3. (25(OH)D. 3. ) levels in 62 consecutive Caucasian patients undergoing total hip replacement for osteoarthritis. The patients were divided into two groups based on whether they were vitamin D sufficient or deficient. The groups were matched for age, gender and the American Society of Anaesthesiologists (ASA) grade. The prevalence of vitamin D deficiency in our patients was comparable with recent population-based studies performed in the United Kingdom. Patients with vitamin D deficiency had lower pre-operative Harris hip scores (Mann-Whitney test, p = 0.018) and were significantly less likely to attain an excellent outcome from total hip replacement (chi-squared test, p = 0.038). Vitamin D levels were found to positively correlate with both pre- and post-operative Harris hip scores. These results warrant further study of vitamin D deficiency in patients undergoing joint replacement as it is a risk factor for a suboptimal outcome which is relatively simple and cheap to correct

This study examined the role of vitamin D as a factor accounting for fatty degeneration and muscle function in the rotator cuff. There were 366 patients with disorders of the shoulder. A total of 228 patients had a full-thickness tear (group 1) and 138 patients had no tear (group 2). All underwent magnetic resonance arthrography and an isokinetic muscle performance test. The serum concentrations of vitamin D (25(OH)D. 3. ) were measured. In general, a lower serum level of vitamin D was related to higher fatty degeneration in the muscles of the cuff. Spearman’s correlation coefficients were 0.173 (p = 0.001), −0.181 (p = 0.001), and −0.117 (p = 0.026) for supraspinatus, infraspinatus and subscapularis, respectively. In group 1, multivariate linear regression analysis revealed that the serum level of vitamin D was an independent variable for fatty degeneration of the supraspinatus and infraspinatus. The serum vitamin D level has a significant negative correlation with the fatty degeneration of the cuff muscle and a positive correlation with isokinetic muscle torque

Serum 1.25 dihydroxyvitamin D concentrations were reduced in elderly patients with femoral neck fractures, irrespective of the presence of osteomalacia. This reduction was not attributable to a decrease in vitamin D binding protein. The low rate of bone turnover in these elderly patients might reduce the requirement for vitamin D and protect against the development of osteomalacia. Serum vitamin D metabolite concentration cannot be used as a screening test for osteomalacia in these patients

Vitamin D metabolite levels were measured in serum and bone samples obtained from 27 patients undergoing elective bony procedures and from 28 patients operated on after a fracture. Serum 25 hydroxyvitamin D3 (25-OH-D3) and 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) did not differ significantly between the elective and fracture patients, but serum 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) was significantly reduced in the fracture patients. Very little 25-OH-D3 was found in bone, although it was the major vitamin D metabolite in serum (90%). In elective patients bone levels of 24,25(OH)2D3 and 1,25(OH)2D3 were similar to those in serum; however, in bone from around pertrochanteric fractures, but not from subcapital or patellar fractures, the concentrations of these compounds were considerably increased. These findings may shed light on the mechanism of callus formation and on the role of vitamin D metabolites in bone healing

When large daily doses of vitamin D were administered to rats endochondral growth was inhibited and bone resorption occurred; later in the process uncalcified matrix (osteoid) like that seen in rickets formed on trabecular margins. When vitamin D was given only for a short period and then discontinued, little resorption of bone was seen during the withdrawal period and wide seams of osteoid material appeared which eventually calcified in an irregular manner. When normal endochondral growth was resumed a wide transverse band of dense bone with enclosed cartilaginous cores was left in the marrow cavity. If, after a few days, a second large dose of the vitamin was given resorption again occurred and calcification of osteoid material was accelerated, the first microscopic sign being a dense, wide, granular, deeply staining line at the junction of the bone and new osteoid. After a second withdrawal period a second layer of osteoid formed; eventually another transverse band appeared in the metaphysis. If this hypervitaminosis D cycle (+4 -12) was continued rats continued to form new bone with relatively little remodelling, so that after three such cycles bones became dense and hard. Histological study showed that little marrow cavity remained in either skull, vertebrae or epiphyses and a dense mass of bone enclosing cartilage cores filled the metaphysial part of the long bones. In addition, ankylosis ofteeth, calcification of spinal ligaments and widespread metastatic calcification were present. When hypervitaminosis D cycles (+1 -12, +1 -21) were adjusted to produce minimal resorptive changes a wide range of bone change was observed. This varied from uniform dense metaphysial bone containing abnormal cartilage matrix arranged in longitudinal striations, dense transverse bands parallel to the epiphysial cartilage, to remnants of dense trabeculae extending into the marrow cavity. Bone changes in osteopetrosis structurally closely resembled the induced bone changes in the rat. It is concluded that an important mechanism in the production of osteopetrosis is an accentuated rhythm of bone change like that shown experimentally to be produced in these animals. It is emphasised that these changes are but part of a range of bone disorders associated with abnormalities of cycles of resorption and deposition of bone, the type of change differing with the nature of the cycles

We investigated the effect of vitamin D receptor gene (VDRG) polymorphism on the responsiveness to 1,25(OH). 2. D. 3. in human osteoblast-like cells. The cells were obtained from the femoral heads of 18 women with osteoarthritis of the hip. Three different restriction enzymes, BsmI, ApaI, and TaqI, were used to analyse the polymorphism. The genotypes of the 18 patients were bbAaTT (8), bbaaTT (6), BbAaTt (3), and BbAATt (1). Our findings showed that there were no differences according to the VDR genotype, but there was a statistically significant difference in the production of osteocalcin between BbAaTt and bbAaTT, and between BbAaTt and bbaaTT. Northern blot analysis of osteocalcin and VDR mRNA showed no significant differences among the three VDR genotypes. These findings suggest that VDR gene polymorphism affects the individual responsiveness of 1,25(OH). 2. D. 3.

A total of 63 women who had an operation for a fracture of the hip was randomly allocated to one year of treatment either with anabolic steroids, vitamin D and calcium (anabolic group) or with calcium only (control group). The thigh muscle volume was measured by quantitative CT. The bone mineral density of the hip, femur and tibia was assessed by quantitative CT and dual-energy x-ray absorptiometry and of the heel by quantitative ultrasound. Quantitative CT showed that the anabolic group did not lose muscle volume during the first 12 months whereas the control group did (p< 0.01). There was less bone loss in the proximal tibia in the anabolic group than in the control group. The speed of gait and the Harris hip score were significantly better in the anabolic group after six and 12 months. Anabolic steroids, even in this moderate dose, given in combination with vitamin D and calcium had a beneficial effect on muscle volume, bone mineral density and clinical function in this group of elderly women

Aims. Despite the COVID-19 pandemic, incidence of hip fracture has not changed. Evidence has shown increased mortality rates associated with COVID-19 infection. However, little is known about the outcomes of COVID-19 negative patients in a pandemic environment. In addition, the impact of vitamin D levels on mortality in COVID-19 hip fracture patients has yet to be determined. Methods. This multicentre observational study included 1,633 patients who sustained a hip fracture across nine hospital trusts in North West England. Data were collected for three months from March 2020 and for the same period in 2019. Patients were matched by Nottingham Hip Fracture Score (NHFS), hospital, and fracture type. We looked at the mortality outcomes of COVID-19 positive and COVID-19 negative patients sustaining a hip fracture. We also looked to see if vitamin D levels had an impact on mortality. Results. The demographics of the 2019 and 2020 groups were similar, with a slight increase in proportion of male patients in the 2020 group. The 30-day mortality was 35.6% in COVID-19 positive patients and 7.8% in the COVID-19 negative patients. There was a potential association of decreasing vitamin D levels and increasing mortality rates for COVID-19 positive patients although our findings did not reach statistical significance. Conclusion. In 2020 there was a significant increase in 30-day mortality rates of patients who were COVID-19 positive but not of patients who were COVID-19 negative. Low levels of vitamin D may be associated with high mortality rates in COVID-19 positive patients. Cite this article: Bone Joint J 2021;103-B(4):782–787

Twenty-three of 46 patients, aged 56 to 95 years, with fracture of the femoral neck (FNF) completed the first trial of 10 months treatment with oral sodium fluoride 60 mg and calcium 1800 mg on alternate days and 1 micrograms of vitamin D1 daily. Pre-treatment and post-treatment biopsy specimens and microradiographs of the iliac crest and metacarpal and spinal radiographs were evaluated together with biopsy material from seven untreated age-matched controls with FNF. In 17 patients the treatment improved the amount and quality of trabecular bone. Cortical thickness increased in nine patients and there were no losses of amount or mineralisation. The treatment was well tolerated by most patients and there were no major side-effects or signs of bone demineralisation. The study also revealed an unexpected rapid post-fracture deterioration of bone tissue in untreated FNF patients; thus there is an increased risk of further fractures which calls for the use of an effective treatment to increase bone mass.

In vitamin D-fed chicks 1,25-dihydroxyvitamin D3 and 24,25-dihydroxyvitamin D3 were implanted into experimentally-produced fractures of the mid-tibia. The mechanical and biochemical properties of the tibia were evaluated for two weeks, including torsion tests, measurement of alkaline phosphatase activity, 45Ca incorporation, and Ca2+ content. Both dihydroxylated metabolites of vitamin D3 had a direct effect on endochondral bone formation. 24,25(OH)2D3 strengthened the callus, and raised alkaline phosphate activity in the first seven days after fracture. 1,25(OH)2D3 decreased the strength of the callus concomitant with a reduction in 45Ca incorporation. It is suggested that local application of 24,25(OH)2D3 into fractures may accelerate healing and prevent non-union.

Aims. To evaluate the effect of a single early high-dose vitamin D supplement on fracture union in patients with hypovitaminosis D and a long bone fracture. Patients and Methods. Between July 2011 and August 2013, 113 adults with a long bone fracture were enrolled in a prospective randomised double-blind placebo-controlled trial. Their serum vitamin D levels were measured and a total of 100 patients were found to be vitamin D deficient (< 20 ng/ml) or insufficient (< 30 ng/mL). These were then randomised to receive a single dose of vitamin D. 3. orally (100 000 IU) within two weeks of injury (treatment group, n = 50) or a placebo (control group, n = 50). We recorded patient demographics, fracture location and treatment, vitamin D level, time to fracture union and complications, including vitamin D toxicity. Outcomes included union, nonunion or complication requiring an early, unplanned secondary procedure. Patients without an outcome at 15 months and no scheduled follow-up were considered lost to follow-up. The t-test and cross tabulations verified the adequacy of randomisation. An intention-to-treat analysis was carried out. Results. In all, 100 (89%) patients had hypovitaminosis D. Both treatment and control groups had similar demographics and injury characteristics. The initial median vitamin D levels were 16 ng/mL (interquartile range 5 to 28) in both groups (p = 0.885). A total of 14 patients were lost to follow-up (seven from each group), two had fixation failure (one in each group) and one control group patient developed an infection. Overall, the nonunion rate was 4% (two per group). No patient showed signs of clinical toxicity from their supplement. Conclusions. Despite finding a high level of hypovitaminosis D, the rate of union was high and independent of supplementation with vitamin D. 3. . Cite this article: Bone Joint J 2017;99-B:1520–5

Aims. As the population ages and the surgical complexity of lumbar spinal surgery increases, the preoperative stratification of risk becomes increasingly important. Understanding the risks is an important factor in decision-making and optimizing the preoperative condition of the patient. Our aim was to determine whether the modified five-item frailty index (mFI-5) and nutritional parameters could be used to predict postoperative complications in patients undergoing simple or complex lumbar spinal fusion. Methods. We retrospectively reviewed 584 patients who had undergone lumbar spinal fusion for degenerative lumbar spinal disease. The 'simple' group (SG) consisted of patients who had undergone one- or two-level posterior lumbar fusion. The 'complex' group (CG) consisted of patients who had undergone fusion over three or more levels, or combined anterior and posterior surgery. On admission, the mFI-5 was calculated and nutritional parameters collected. Results. Complications occurred in 9.3% (37/396) of patients in the SG, and 10.1% (19/167) of patients in the CG. In the SG, the important predictors of complications were age (odds ratio (OR) 1.036; p = 0.002); mFI-5 (OR 1.026 to 2.411, as score increased to 1 ≥ 2 respectively. ;. p = 0.023); albumin (OR 11.348; p < 0.001); vitamin D (OR 2.185; p = 0.032); and total lymphocyte count (OR 1.433; p = 0.011) . In the CG, the predictors of complications were albumin (OR 9.532; p = 0.002) and vitamin D (OR 3.815; p = 0.022). Conclusion. The mFI-5 and nutritional status were effective predictors of postoperative complications in the SG, but only nutritional status was successful in predicting postoperative complications in the CG. The complexity of the surgery, as well as the preoperative frailty and nutritional status of patients, should be considered when determining if it is safe to proceed with lumbar spinal fusion. Cite this article: Bone Joint J 2020;102-B(12):1717–1722

Aims. Prosthetic joint infection (PJI) remains a serious complication that is associated with high morbidity and costs. The aim of this study was to prepare a systematic review to examine patient-related and perioperative risk factors that can be modified in an attempt to reduce the rate of PJI. Materials and Methods. A search of PubMed and MEDLINE was conducted for articles published between January 1990 and February 2018 with a combination of search terms to identify studies that dealt with modifiable risk factors for reducing the rate of PJI. An evidence-based review was performed on 12 specific risk factors: glycaemic control, obesity, malnutrition, smoking, vitamin D levels, preoperative Staphylococcus aureus screening, the management of anti-rheumatic medication, perioperative antibiotic prophylaxis, presurgical skin preparation, the operating room environment, irrigant options, and anticoagulation. Results. Poor glycaemic control, obesity, malnutrition, and smoking are all associated with increased rates of PJI. Vitamin D replacement has been shown in preliminary animal studies to decrease rates of PJI. Preoperative Staphylococcus aureus screening and appropriate treatment results in decreased rates of PJI. Perioperative variables, such as timely and appropriate dosage of prophylactic antibiotics, skin preparation with chlorohexidine-based solution, and irrigation with dilute betadine at the conclusion of the operation, have all been associated with reduced rates of PJI. Similarly, aggressive anticoagulation and increased operating room traffic should be avoided to help minimize risk of PJI. Conclusion. PJI remains a serious complication of arthroplasty. Surgeons should be vigilant of the modifiable risk factors that can be addressed in an attempt to reduce the risk of PJI

Aims. Bone health assessment and the prescription of medication for secondary fracture prevention have become an integral part of the acute management of patients with hip fracture. However, there is little evidence regarding compliance with prescription guidelines and subsequent adherence to medication in this patient group. Patients and Methods. The World Hip Trauma Evaluation (WHiTE) is a multicentre, prospective cohort of hip fracture patients in NHS hospitals in England and Wales. Patients aged 60 years and older who received operative treatment for a hip fracture were eligible for inclusion in WHiTE. The prescription of bone protection medications was recorded from participants’ discharge summaries, and participant-reported use of bone protection medications was recorded at 120 days following surgery. Results. Of 5456 recruited patients with baseline data, 2853 patients (52%) were prescribed bone protection medication at discharge, of which oral bisphosphonates were the most common, 4109 patients (75%) were prescribed vitamin D or calcium, and 606 patients (11%) were not prescribed anything. Of those prescribed a bone protection medication, only 932 patients (33%) reported still taking their medication 120 days later. Conclusion. These data provide a reference for current prescription and adherence rates. Adherence with oral medication remains poor in patients with hip fracture. Cite this article: Bone Joint J 2019;101-B:1402–1407

1. A child is described who presented with very severe rickets and gross myopathy. The clinical, biochemical and radiological signs were identical with those to be expected of a very chronic and severe vitamin D deficiency. The child's diet, however, had been normal. 2. All the pathological signs, except for residual dwarfism and leg bowing, disappeared on treatment with very large doses of vitamin D. 2. Ordinary anti-rachitic doses had no effect. 3. We suggest that this child demonstrates a true resistance to the action of vitamin D and that the defect is permanent. The findings in two similar patients that we have seen suggest that the condition is inherited as an autosomal recessive gene, and that it may be the same disease as that described in the continental literature as "hereditäre pseudo-mangelrachitis" and by other names. 4. The disease seems distinct clinically and biochemically from the disease originally described under the name "vitamin resistant rickets," which does not respond so well to massive vitamin D therapy and which is usually inherited as a sex-linked dominant gene

1. A clinical, radiological and histological description of a patient with fibrogenesis imperfecta ossium is given. We think that this is the first case in which diagnosis has been made during the life of the patient. 2. The disease is characterised by a defect in the formation of the collagen fibres of the bone matrix. There is also a failure of normal calcification of the matrix, giving rise to the appearance of wide "osteoid" seams. When examined with the polarising microscope and when stained with Gomori's reticulin stain the collagen fibres can be seen to be grossly deficient and abnormal. 3. The patient presented at the age of fifty-four years with bone pain and multiple fractures. The only biochemical abnormality detected in the plasma was an elevated alkaline phosphatase. He was also in negative calcium balance. 4. Treatment with vitamin D. 2. , later changed to dihydrotachysterol, appears to have produced clinical, biochemical and radiological improvement. It appears that a direct action of the vitamin on the abnormal bone collagen must be postulated, in addition to its known actions on the calcifying mechanisms. 5. An unusual feature of the case was the slow development of a total unresponsiveness to large doses of vitamin D. 2. , in spite of a markedly elevated level of vitamin D in the plasma. There was later a response to a much smaller dose of dihydrotachysterol, which is being maintained to date

Slipped capital femoral epiphysis (SCFE) is uncommon in India and we routinely look for associated metabolic or endocrine abnormalities. In this study we investigated a possible association between vitamin D deficiency and SCFE. All children presenting with SCFE during the study period had their 25-hydroxyvitamin D levels measured as part of an overall metabolic, renal and endocrine status evaluation, which included measurement of body mass index (BMI). Vitamin D status was compared with age-, gender- and habitat-matched controls with acute trauma or sepsis presenting to our emergency department. A total of 15 children (12 boys and three girls) with a mean age of 13 years (. sd. 1.81; 10 to 16) presented for treatment for SCFE during a two-year period beginning in January 2010. Renal and thyroid function was within the normal range in all cases. The mean BMI was 24.9 kg/m. 2. (17.0 to 33.8), which was significantly higher than that of the controls (p = 0.006). There was a statistically significant difference between the mean values of 25-hydroxyvitamin D in the children with SCFE and the controls (11.78 ng/ml (. sd. 5.4) versus 27.06 ng/ml (. sd. 5.53), respectively; p < 0.001). We concluded that, along with high BMI, there is a significant association of vitamin D deficiency and SCFE in India. Cite this article: Bone Joint J 2013;95-B:851–4