Multiple Looser zones of osteomalacia in Byler disease with associated vitamin D deficiency, phosphaturia, and elevated FGF23.

INTRODUCTION: Byler disease (progressive familial intrahepatic cholestasis) is associated metabolic bone disease as a consequence of chronic malabsorption. CASE PRESENTATION: A 33-year-old man with decompensated liver disease secondary to Byler disease was referred to the orthopaedic department with progressive pain over this right proximal tibia. On examination, he had an antalgic gait. Tenderness was localised to the proximal tibia just distal to the tibial tubercle and bilateral foot swelling. Radiographs showed multiple stress fractures characteristic of Looser zones at various stages of healing in both tibia, metatarsals (third, fourth, and fifth on the right side, and second and fourth on the left) and left femur. Bone mineral density was extremely low. Subsequent investigations were consistent with severe osteomalacia due to a combination of vitamin D deficiency and phosphaturia with elevated fibroblast factor 23 (FGF23). A good clinical response was achieved following supplementation with calcium 1000mg and vitamin D 20µg daily. DISCUSSION: Stress fractures are often associated with delay in diagnosis. Our patient presented to the orthopaedic service with multiple Looser zones that had not been previously detected. As expected, there was biochemical evidence of vitamin D deficiency. An unexpected finding was phosphaturia that was associated with marked elevation in FGF23, which has never been reported previously. CONCLUSION: Byler disease may result in Looser zones of osteomalacia due to chronic malabsorption. Renal phosphorus wasting as a consequence of unexplained marked elevation in FGF23 is thought to have contributed to the onset of osteomalacia.

Correction of vitamin D deficiency in a cohort of newborn infants using daily 200 IU vitamin D supplementation.

INTRODUCTION: Although the role of vitamin D in the prevention of rickets has long been well established, controversies still exist on the ideal dose of vitamin D supplementation in infants. OBJECTIVE: We assessed serum 25-hydroxyvitamin D (25OHD) status simultaneously in maternal and cord samples and the response to vitamin D3 supplementation in neonates. METHODS: Serum 25OHD levels were evaluated from maternal, and umbilical cord samples from term normal pregnancies. Repeat 25OHD levels were assessed in neonates with 25OHD below 30 nmol/L following vitamin D3 200 IU daily after 6 weeks. RESULTS: Blood samples were taken including 57 cord samples and 16 follow-up neonatal samples. Maternal and cord serum 25OHD were 43 ± 21 and 29 ± 15 nmol/L, respectively. Infants with 25OHD < 30 nmol/L (19.8 ± 4.7 nmol/L) had a significant increase in serum 25OHD (63.3 ± 14.5 nmol/L) following vitamin D3 200 IU daily after 6 weeks. CONCLUSION: Healthy Irish infants born at term are at high risk of vitamin D deficiency, but vitamin D3 200 IU daily, rapidly corrects poor vitamin D status.

The double-edged sword of vitamin D in Ireland: the need for public health awareness about too much as well as too little.

INTRODUCTION: The Institute of Medicine (IOM) 2011 on dietary references intakes for calcium and vitamin D specified that a 25-hydroxyvitamin D (25OHD) level below 30 nmol/L indicated risk of deficiency and that a level above 125 nmol/L indicated risk of harm. METHODS: We noted a high prevalence of hypovitaminosis D (23.9 %) and a substantive prevalence of hypervitaminosis D (4.8 %) in a retrospective audit of clinical samples (n = 10,181) obtained over 10 months in 2013. CONCLUSION: Hypovitaminosis D should be corrected by low dose supplementation (5 µg or 200 IU daily) with some at-risk groups needing higher doses (10 µg or 400 IU daily) based on 25OHD levels. Whereas, those taking high-dose vitamin D supplements based on mistaken beliefs about recently authorised claims of benefit for muscle function and misleading unauthorised claims need to be alerted to the potential harms of excessive supplementation.

Association between vitamin D status and physical function in the severely obese.

CONTEXT: Mortality is 85% higher in severely obese subjects (body mass index [BMI] > 40 kg/m(2)) than in subjects with a healthy BMI; poor physical function may be contributory. Hypovitaminosis D is common in obese subjects and is associated with physical dysfunction in the elderly. OBJECTIVE: We determined the relationship between vitamin D status and physical function in severely obese subjects. DESIGN, SETTING, AND PATIENTS: We conducted a clinic-based, cross-sectional study of severely obese subjects. Participants were stratified into three groups according to the Institute of Medicine (IOM) vitamin D status categorization. MAIN OUTCOME MEASURES: We compared levels of self-reported activity and times taken to walk 500 m and to ascend and descend a 17-cm step 50 times. RESULTS: We recruited 252 subjects (age, 43.7 ± 11.2 y; BMI, 50.7 ± 9.7 kg/m(2)); 25-hydroxyvitamin D (25OHD) concentrations were less than 30 nmol/L in 109 participants. Participants with a 25OHD > 50 nmol/L, compared to those with a 25OHD < 30 nmol/L, had the highest activity levels (3.1 ± 3.4 h/wk versus 1.5 ± 2.5 h/wk; P = .015) and the shortest 500-m walk times (6.2 ± 1.1 min versus 7.4 ± 1.5 min; P = .003). Serum 25OHD concentrations had a weakly positive association with activity level (r = 0.19; P = .008) and a moderately negative association with 500-m walk time (r = -0.343; P < .001). CONCLUSIONS: Vitamin D status had a significant relationship with physical activity and physical function in this cohort of severely obese subjects. Low activity levels are likely to perpetuate the problem of hypovitaminosis D due to less time spent outdoors. Studies exploring the effects of vitamin D supplementation in this population are warranted.

Limited utility of tartrate-resistant acid phosphatase isoform 5b in assessing response to therapy in osteoporosis.

BACKGROUND: Tartrate-resistant acid phosphatase isoform 5b (TRACP5b) is a serum bone resorption marker. Our aim was to investigate its utility in monitoring metabolic bone disease. METHODS: Serum TRACP5b, C-terminal cross-linking telopeptide of type I collagen, urine N-terminal cross-linking telopeptide of type I collagen and free deoxypyridinoline were measured pre- and post-treatment with a parathyroid hormone analogue [PTH (1-34)] (n = 14) or a bisphosphonate (N-BP) (n = 8). TRACP5b, bone alkaline phosphatase (bone ALP), 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) were measured in 100 osteoporosis patients on prolonged bisphosphonate therapy. RESULTS: Changes in TRACP5b were smaller in magnitude but mimicked those of other bone resorption markers. Absolute changes in TRACP5b and the other resorption markers correlated significantly (p < 0.001). In patients on long-term bisphosphonates, TRACP5b and bone ALP levels were not suppressed. Vitamin D status was consistent with the level of supplementation. CONCLUSION: TRACP5b has limited utility as a single marker of metabolic bone disease treatment.

Relationship between vitamin D knowledge and 25-hydroxyvitamin D levels amongst pregnant women.

BACKGROUND: Pregnant women living at northerly latitudes are at risk of suboptimal vitamin D status. There is a paucity of studies correlating knowledge, attitudes and practices of vitamin D with serum levels amongst pregnant women. We aimed to determine the prevalence of suboptimal vitamin D status in pregnant women of various ethnicities attending two Dublin maternity hospitals and to assess levels of knowledge, attitudes and practices concerning vitamin D. METHODS: We conducted a cross-sectional study of 116 pregnant women of Irish, Asian, Sub-Saharan African and Middle Eastern and North African (MENA) origin. Vitamin D status was determined by measurement of serum 25-hydroxyvitamin D (25OHD). We examined knowledge, attitudes and practices concerning vitamin D using an interview-assisted questionnaire. RESULTS: The median (interquartile range) 25OHD level was 25.9 (16.5-44.7) nmol L(-1). Using a cut-off point of <30 nmol L(-1) , the proportion at risk of deficiency was significantly higher among MENA (88%; P < 0.001) and Sub-Saharan African women (68%; P = 0.019) than Irish women (36%). Eighty-two women (71%) reported they had insufficient knowledge about vitamin D and its sources. Vitamin D containing supplement usage was the strongest predictor of 25OHD levels ≥30 nmol L(-1) (odds ratio = 18.03, 95% confidence interval = 5.7256.8, P < 0.001). CONCLUSIONS: Suboptimal vitamin D status is common in this cohort of pregnant women, especially among those of Sub-Saharan African and MENA origin. Awareness of vitamin D dietary sources is poor among all subgroups. Recommending vitamin D containing supplements may be the best strategy at present for improving vitamin D status with a need for increased vitamin D education.