In vitro osteoclastogenesis from Gaucher patients' cells correlates with bone mineral density but not with Chitotriosidase.

Gaucher disease (GD) is caused by mutations on the gene encoding for the lysosomal enzyme glucocerebrosidase. Type I GD (GD1) patients present anemia, hepatosplenomegaly and bone alterations. In spite of treatment, bone alterations in GD patients persist, including poor bone mineral density (BMD). Mechanisms leading to bone damage are not completely understood, but previous reports suggest that osteoclasts are involved. Chitotriosidase (CHIT) is the most reliable biomarker used in the follow up of patients, although its correlation with bone status is unknown. The aim of this work was to study the pro-osteoclastogenic potential in patients and to evaluate its correlation with CHIT activity levels and clinical parameters. PBMCs from treated patients and healthy controls were cultured in the presence of M-CSF, and mature osteoclasts were counted. BMD, blood CHIT activity and serum levels of CTX, BAP, and cytokines were evaluated in patients. We found that blood CHIT activity and osteoclast differentiation were significantly increased in patients, but no correlation between them was observed. Interestingly, osteoclast numbers but not CHIT, presented a negative correlation with BMD expressed as Z-score. CTX, BAP and serum cytokines involved in bone remodeling were found altered in GD1 patients. These results show for the first time a correlation between osteoclast differentiation and BMD in GD1 patients, supporting the involvement of osteoclasts in the bone pathology of GD1. Our results also suggest that an altered immune response may play an important role in bone damage.

Effect of Denosumab on Bone Mineral Density and Markers of Bone Turnover among Postmenopausal Women with Osteoporosis.

The aim of this study was to evaluate the effect of denosumab (Dmab) on bone mineral density (BMD) and bone turnover markers after 1 year of treatment. Additionally, the effect of Dmab in bisphosphonate-naïve patients (BP-naïve) compared to patients previously treated with bisphosphonates (BP-prior) was analyzed. This retrospective study included 425 postmenopausal women treated with Dmab for 1 year in clinical practice conditions in specialized centers from Argentina. Participants were also divided according to previous bisphosphonate treatment into BP-naïve and BP-prior. A control group of patients treated with BP not switched to Dmab matched by sex, age, and body mass index was used. Data are expressed as mean ± SEM. After 1 year of treatment with Dmab the bone formation markers total alkaline phosphatase and osteocalcin were significantly decreased (23.36% and 43.97%, resp.), as was the bone resorption marker s-CTX (69.61%). Significant increases in BMD were observed at the lumbar spine, femoral neck, and total hip without differences between BP-naïve and BP-prior. A better BMD response was found in BP-prior group compared with BP treated patients not switched to Dmab. Conclusion. Dmab treatment increased BMD and decreased bone turnover markers in the whole group, with similar response in BP-naïve and BP-prior patients. A better BMD response in BP-prior patients versus BP treated patients not switched to Dmab was observed.

Vitamin D3 seems more appropriate than D2 to sustain adequate levels of 25OHD: a pharmacokinetic approach.

BACKGROUND/OBJECTIVES: The superiority of cholecalciferol (D3) over ergocalciferol (D2) in sustaining serum 25-hydroxy vitamin D (25OHD) levels is controversial. To compare D2 with D3 we performed a single-blind, placebo-controlled randomized trial spanning 11 weeks. SUBJECTS/METHODS: Healthy volunteers (n=33, aged 33.4±6 years) were divided into three groups (n=11, each): D2, D3 and placebo. Treatment started with a loading dose (100,000 IU) followed by 4800 IU/day (d) between d7 and d20 and follow-up until d77. Serum samples were obtained at baseline and at days 3, 7, 14, 21, 35, 49, 63 and 77. RESULTS: Baseline 25OHD values in the D2 group were lower than those in the D3 and placebo groups (P<0.01). Placebo 25OHD levels never changed. As after the loading dose both D2 and D3 groups had reached similar 25OHD levels, we tested equivalence of the area under the concentration × time curve (AUC) between d7 and d77. The AUC was 28.6% higher for D3 compared with D2, and both were higher with respect to placebo. At d77, D2 25OHD levels were higher than those at baseline, but similar to placebo; both were lower than D3 (P<0.04). According to raw data, the elimination half-life of 25OHD was 84 and 111 days under D2 and D3 supplementation, respectively; after subtracting the placebo values, the corresponding figures were 33 and 82 days. CONCLUSIONS: D2 and D3 were equally effective in elevating 25OHD levels after a loading dose. In the long term, D3 seems more appropriate for sustaining 25OHD, which could be relevant for classic and non-classic effects of vitamin D.

Effect of vitamin D nutritional status on muscle function and strength in healthy women aged over sixty-five years.

BACKGROUND: Vitamin D insufficiency is common in elderly adults, and leads to secondary hyperparathyroidism, bone loss, muscle weakness, and osteoporotic fractures. OBJECTIVE: To evaluate the relation between vitamin D nutritional status and muscle function and muscle strength in women aged over 65 years. METHODS: Fifty-four postmenopausal women from Buenos Aires (latitude 34° S), average age (X±DS) 71±4, were included in the study. Determinations of serum calcium, phosphate, 25 hydroxyvitamin D (25OHD), intact parathormone (iPTH) and calciuria / creatininuria ratio in 24-hour urine samples were performed. Muscle function was assessed by means of walking-speed test, standing balance, and sit-to-stand tests. Lower extremity muscle strength was determined using a manual dynamometer. RESULTS: 25OHD levels ≥20 ng/ml were found to be associated with better lower extremity muscle function and strength. Forty- six % of participants had 25OHD levels ≥20 ng/ml. Women with 25OHD levels ≥20 ng/ml scored higher on the muscle function tests (11.2±0.9 vs.10.0±2.1; p<0.003) and had stronger knee extensor (13.4±2.7 vs.11.6±2.5 Kg.; p<0.03) and hip abductor (8.3±2.7 vs. 7.3±3.1 Kg; p<0.04) muscles; strength of their hip flexors tended to be higher but did not reach significantly different values (17.0±3.3 vs. 15.4±2.8 Kg.; 0.1>p>0.05). Negative correlation was observed between iPTH and muscle function (r= -0.436; p<0.02). CONCLUSION: 25OHD levels ≥20 ng/ml are needed for a better muscle function and strength. Assessing vitamin D nutritional status in adults aged ≥ 65 years would allow correcting hypovitaminosis D and improve muscle function and strength.

Intravenous bisphosphonate treatment and pregnancy: its effects on mother and infant bone health.

INTRODUCTION: Type 1 Gaucher's disease (GD1) is a lysosomal storage disorder associated with disabling bone involvement. The choice treatment for Gaucher's disease is enzyme replacement therapy (ERT). The use of bisphosphonate treatment for osteopenia and osteoporosis has been suggested. CASE: A 22-year-old woman diagnosed with GD1 had received ERT intermittently, depending on availability of the enzyme since the enzyme was not always available. Due to severe bone involvement and multiple vertebral fractures, intravenous administration of 60 mg of pamidronate every 3 months and safe contraception were indicated. Fifteen days after receiving the fourth infusion, the patient informed us she was pregnant. A baby girl was born by cesarean delivery at week 37, showing no evidence of skeletal abnormality or clinical signs of hypocalcemia. The baby developed normally, presenting no significant pathology. At present (age 15 months), height, body weight, and bone mineral density by DXA are within normal range. The mother showed stable total skeleton and right femoral neck bone mineral density (BMD) values, no new fractures, and only ~3% decrease in lumbar spine BMD 15 months post-delivery and after a 1 year breastfeeding period (expected average ~7-8%). CONCLUSION: It could be posited that pamidronate exerted a positive protective effect on the mother's skeleton with no evidence of adverse effects on pregnancy or on the baby's health to date.

Epidemiology of hip fracture in Tucuman, Argentina.

UNLABELLED: The incidence of osteoporotic hip fracture was studied previously in a central area of Argentina. Studying Tucuman (north area) was very useful to compare results of the different areas and detect a similar incidence in women and a slightly higher incidence in men compared with previous data for the central region. INTRODUCTION/METHODS: Epidemiology of hip fracture was studied over a 1-year period in the city of San Miguel de Tucumán (SMT) and in the whole province of Tucumán, located in the northeast of Argentina (latitudes 26° and 28° south). The results were compared with previous studies performed in the central region of Argentina. RESULTS: Two hundred and eighty-three patients (208 women and 75 men) aged 50 years or over in SMT suffered a hip fracture. The incidence in females and males was 334.9 and 163.8 hip fractures per 100,000 inhabitants per year, respectively (female/male ratio 2.0). A total of 498 hip fractures were recorded in Tucuman province (367 in women and 131 in men). The results in females and males were 276.5 and 114.7 hip fractures per 100,000 inhabitants per year, respectively. Average age of the female and male population was 78±9 and 77±9 years, respectively. CONCLUSIONS: These results showed that the incidence of hip fracture in female and male populations in SMT was similar to previous studies performed in the central area of the country. Further studies on the south area of Argentina should be conducted to complete the information on a large country extending from latitudes 22° to 55°S.

Body composition and bone metabolism in young Gaucher disease type I patients treated with imiglucerase.

UNLABELLED: Bone involvement is one of the most disabling complications in patients with type 1 Gaucher disease (GDI) and its pathophysiology is yet to be fully understood. It is well known that body composition is a determinant of bone mass. Previous reports indicating disturbance in glucose and lipid metabolism in GDI patients suggested a posible alteration in body composition in this group of patients. OBJECTIVE: To analyze body composition, bone mass and turnover in young adults with GDI receiving enzyme replacement therapy (ERT). POPULATION: 5 women and 4 men with GDI aged (X +/- SD) 26.9 +/- 6.9 years, receiving imiglucerase in a mean dose of 53 +/- 13 IU/kg/2weeks, during 4.9 +/- 3.9 years; and 145 sex and age matched healthy adults agreed to participate in the study. All control subjects had a body mass index (BMI) between 20 and 25 kg/m2. METHODS: Total body dual X-ray absorptiometry (DXA) was used to measure body composition and bone mass. Serum creatinine, calcium, osteocalcin (BGP), and type I collagen beta carboxy-terminal telopeptide (betaCTX) were determined in patients and controls. In addition, 25 hydroxyvitamin D (25OHD), and chitotriosidase activity were measured in patients. RESULTS: GDI patients presented statistically significant (p<0.01) lower BMI, bone mineral density (BMD), bone mineral content (BMC), lean mass (LM), and fat mass (FM), compared to controls. LM correlated positively with BMC and BMD in both groups (p<0.01). GDI patients receiving the lower dose of ERT (<60 IU/kg/2weeks) presented lower BMD values than those receiving the higher dose (> or =60 IU/kg/2weeks) (0.968 +/- 0.032 vs 1.088 +/- 0.061 g/m2, respectively, p<0.001). Mean BGP levels were similar in patients and controls, whereas betaCTX levels were higher in GDI patients (p<0.02). All patients presented deficiency levels (<30ng/ml) of 25OHD. CONCLUSIONS: Although the patients had been receiving ERT, they presented a significant diminution in all body composition parameters, the decrease was more evident in those receiving the lower dose. The reduction in bone mass was associated with an imbalance in bone turnover (increased bone resorption). The correlation between LM and bone mass, suggests that metabolic disturbance occurring in GDI patients may be indirectly responsible for bone mass reduction in GDI patients, by altering body composition.

Vitamin D2 dose required to rapidly increase 25OHD levels in osteoporotic women.

OBJECTIVE: Assessment of the effectiveness and safety of high daily 125 microg (5,000 IU) or 250 microg (10,000IU) doses of vitamin D(2) during 3 months, in rapidly obtaining adequate 25 hydroxyvitamin D (25OHD) levels. DESIGN: Longitudinal study. SUBJECTS: Postmenopausal osteopenic/osteoporotic women (n = 38) were studied during winter and spring. Median age (25-75th percentile) was 61.5 (57.00-66.25) years, and mean bone mineral density (BMD) was 0.902 (0.800-1.042)g/cm(2). Subjects were randomly divided into three groups: control group (n=13): no vitamin D(2), 125 mug/day (n=13) and 250 microg/day (n=12) of vitamin D(2) groups, all receiving 500 mg calcium/day. Serum calcium, phosphate, bone alkaline phosphatase (BAP), C-telopeptide (CTX), 25OHD, mid-molecule parathyroid hormone (mmPTH), daily urinary calcium and creatinine excretion were determined at baseline and monthly. RESULTS: For all subjects (n=38), the median baseline 25 hydroxyvitamin D (25OHD) level was 36.25 (27.5-48.12) nmol/l. After 3 months, 8% of the patients in the control group, 50% in the 125 microg/day group and 75% in the 250 microg/day group had 25OHD values above 85 nmol/l (34 ng/ml). Considering both vitamin D(2) groups together, mmPTH and BAP levels diminished significantly after 3 months (P<0.02), unlike those of CTX. Serum calcium remained within normal range during the follow-up. CONCLUSIONS: The oral dose of vitamin D(2) required to rapidly achieve adequate levels of 25OHD is seemingly much higher than the usual recommended vitamin D(3) dose (20 mug/day). During 3 months, 250 microg/day of vitamin D(2) most effectively raised 25OHD levels to 85 nmol/l in 75% of the postmenopausal osteopenic/osteoporotic women treated.

Telopeptido carboxilo terminal del colageno tipo i ( beta-ctx ) serico y / compromiso oseo en la insuficiencia renal cronica / Serum beta-type I collagen carboxyterminal telopeptide ( beta-CTXs ) and bone involvement in chronic renal failure

La osteodistrofia renal (ODR) se caracteriza por alteraciones óseas. Se evaluaron métodos bioquímicosalternativos a la biopsia ósea en pacientes renales para determinar cambios rápidos delremodelamiento óseo en 43 pacientes predialíticos (PD) y 49 hemodializados (HD). Los PD presentaronfosfatemia, fosfatasa alcalina ósea (FAO), hormona paratiroidea intacta (PTHi) y beta-telopéptido carboxilo terminaldel colágeno tipo I (betaCTXs) mayores y clearence de creatinina (Ccr) menores (p<0.001) que los controles.La fosfatemia de HD fue más elevada, significativamente respecto de controles (p<0.0001); FAO, PTHi y betaCTXsfueron mayores a los otros dos grupos (p<0.0001). En ambos grupos renales betaCTXs y FAO correlacionaroncon PTHi (p<0.002 y p<0.0001, respectivamente) y entre sí (p<0.0001). Los PD con Ccr <40 ml/min presentaronPTHi, FAO y bCTXs (p<0.004, p<0.05 y p<0.001, respectivamente) más elevados que aquellos con Ccr>40ml/min. En PD, betaCTXs (p<0.05) y en HD tanto betaCTXs como FAO (p<0.0001) estaban aumentados respecto decontroles, aun con PTHi normal. Los incrementos mayores en los marcadores óseos se observaron en los pacientescon mayores niveles de PTHi (p<0.001). En conclusión; aun sin PTHi elevada existe un aumento deresorción ósea (posiblemente por otros factores) y la medición de betaCTXs sería una herramienta apropiada notraumática para detectar tempranamente alteraciones óseas por IR que permitiría tomar medidas preventivaspara evitar dicha pérdida. Asimismo, instalada la ODR determinar el aumento del remodelamiento sería sumamenteútil para identificar pacientes que requieran biopsia ósea. El reemplazo de la misma por beta-CTX séricodeberá esperar estudios que demuestren la correlación existente entre ambas metodologías.

Telopeptido carboxilo terminal del colageno tipo i ( beta-ctx ) serico y / compromiso oseo en la insuficiencia renal cronica / Serum beta-type I collagen carboxyterminal telopeptide ( beta-CTXs ) and bone involvement in chronic renal failure

La osteodistrofia renal (ODR) se caracteriza por alteraciones óseas. Se evaluaron métodos bioquímicosalternativos a la biopsia ósea en pacientes renales para determinar cambios rápidos delremodelamiento óseo en 43 pacientes predialíticos (PD) y 49 hemodializados (HD). Los PD presentaronfosfatemia, fosfatasa alcalina ósea (FAO), hormona paratiroidea intacta (PTHi) y beta-telopéptido carboxilo terminaldel colágeno tipo I (betaCTXs) mayores y clearence de creatinina (Ccr) menores (p<0.001) que los controles.La fosfatemia de HD fue más elevada, significativamente respecto de controles (p<0.0001); FAO, PTHi y betaCTXsfueron mayores a los otros dos grupos (p<0.0001). En ambos grupos renales betaCTXs y FAO correlacionaroncon PTHi (p<0.002 y p<0.0001, respectivamente) y entre sí (p<0.0001). Los PD con Ccr <40 ml/min presentaronPTHi, FAO y bCTXs (p<0.004, p<0.05 y p<0.001, respectivamente) más elevados que aquellos con Ccr>40ml/min. En PD, betaCTXs (p<0.05) y en HD tanto betaCTXs como FAO (p<0.0001) estaban aumentados respecto decontroles, aun con PTHi normal. Los incrementos mayores en los marcadores óseos se observaron en los pacientescon mayores niveles de PTHi (p<0.001). En conclusión; aun sin PTHi elevada existe un aumento deresorción ósea (posiblemente por otros factores) y la medición de betaCTXs sería una herramienta apropiada notraumática para detectar tempranamente alteraciones óseas por IR que permitiría tomar medidas preventivaspara evitar dicha pérdida. Asimismo, instalada la ODR determinar el aumento del remodelamiento sería sumamenteútil para identificar pacientes que requieran biopsia ósea. El reemplazo de la misma por beta-CTX séricodeberá esperar estudios que demuestren la correlación existente entre ambas metodologías. (AU)

Low levels of endogenous estradiol protect bone mineral density in young postmenopausal women.

OBJECTIVE: Low levels of endogenous estrogens may play a role in the protection of bone mineral density (BMD) in healthy postmenopausal women. The aim of this study was to evaluate the effect of endogenous estradiol and testosterone on bone mass in young and older healthy postmenopausal women. METHODS: The study involved 99 postmenopausal women aged 55-75 years. The BMDs of the lumbar spine, proximal femur and total skeleton were determined. Measurements were taken of serum calcium, bone alkaline phosphatase, Crosslaps, estradiol, estrone, sex hormone binding globulin, testosterone, bioavailable testosterone and urine calcium. Estradiol was measured using a sensitive assay with a lower detection limit at 5 pg/ml. RESULTS: A multivariate analysis showed that the BMD of the lumbar spine was significantly predicted by estradiol (p < 0.05), and testosterone (p < 0.0001). Likewise, testosterone was found to be an independent predictor of the BMD of the total femur (p < 0.001) and the total skeleton (p < 0.001). The population was divided into two groups: < or = 65 (Group 1) and > 65 years (Group 2) of age and also stratified according to estradiol levels: > 10 and < or = 10 pg/ml. Significant differences in BMD were found in women in Group 1 in whom estradiol levels higher than 10 pg/ml were associated with a higher BMD of the lumbar spine (+ 14%, p < 0.01), proximal femur (+ 6%, p < 0.05) and total skeleton (+ 7%, p < 0.05) compared with women with estradiol levels below 10 pg/ml. Bone alkaline phosphatase levels (p < 0.05) and serum Crosslaps (not significant) were lower in women in Group 1 with a level of estradiol more than 10 pg/ ml. CONCLUSION: Endogenous estradiol levels higher than 10 pg/ml and testosterone protected bone mass in healthy postmenopausal women under 65 years of age. These results were not observed in the group of older women.

Long-term control of hypercalcaemia in an infant with williams-Beuren syndrome after a single infusion of biphosphonate (Pamidronate).

AIM: To report the efficacy of Pamidronate to treat hypercalcaemia in a patient with Williams-Beuren syndrome (WBS). RESULTS: We report a 14-mo-old male infant presenting hypercalcaemia, elfin face and other dysmorphological features of WBS, confirmed by the FISH fluorescent test. Due to the marked symptomatic hypercalcaemia, 13.0 mg/dl intravenous Pamidronate was administered in a single dose of 1 mg/kg. Two days later, serum calcium diminished to normal levels, and remained within normal range during 12 mo follow-up. CONCLUSION: Pamidronate appears to be effective in paediatric patients with WBS and hypercalcaemia.

High prevalence of vitamin D insufficiency in healthy elderly people living at home in Argentina.

OBJECTIVE: To evaluate the nutritional status of vitamin D in urban populations of healthy elderly people living at home, in different regions of Argentina. DESIGN: Cross-sectional study. SUBJECTS: In total, 386 ambulatory subjects over 65 y of age from seven cities (between latitude 26 degrees S and 55 degrees S) were asked to participate between the end of winter and the beginning of spring. Of these, 369 accepted, 30 were excluded because of medical history or abnormal biochemical determinations. Finally, 339 subjects (226 women and 113 men) (X+/-s.d.) (71.3+/- 5.2 y) were included. RESULTS: Serum 25OHD levels were lowest in the South (latitude range: 41 degrees S-55 degrees S): 14.2+/-5.6 ng/ml (P<0.0001vs North and Mid regions); highest in the North (26 degrees S-27 degrees S): 20.7+/-7.4 ng/ml (P<0.03 vs Mid, P<0.0001vs South); and intermediate in the Mid region (33 degrees S-34 degrees S) 17.9+/-8.2 ng/ml. Serum mid-molecule PTH (mmPTH) and 25OHD were inversely related: (r=-0.24, P<0.001). A cutoff level of 25OHD at which serum mmPTH levels began to increase was established at 27 ng/ml. A high prevalence (87-52%) of subjects with 25OHD levels in the deficiency-insufficiency range (25OHD levels <20 ng/ml) was detected. CONCLUSION: This study shows that vitamin D deficiency/insufficiency in the elderly is a worldwide problem. Correction of this deficit would have a positive impact on bone health of elderly people.

Effect of doxercalciferol (1alpha-hydroxyvitamin D2) on PTH, bone turnover and bone mineral density in a hemodialysis patient with persistent secondary hyperparathyroidism post parathyroidectomy.

The efficacy and safety of the vitamin D analog, doxercalciferol (1alpha-hydroxyvitamin D2, 1alphaD2) in the treatment of secondary hyperparathyroidism in hemodialysis patients has been previously reported. We report these effect of 16-week 1alphaD2 treatment on mineral metabolism and bone mineral density (BMD) in a hemodialysis patient with persistent secondary hyperparathyroidism post parathyroidectomy, resistant to previous calcitriol treatment. Levels of iPTH, bone-specific alkaline phosphatase and serum type I collagen C telopeptide were above normal at baseline and were substantially decreased with 1alphaD2 treatment (-92%, -63% and -53%, respectively). BMD increased in all areas: total skeleton (+6.5%), lumbar spine (+6.9%) and total femur (+4.3%). The patient showed no hypercalcemia, and phosphorus levels remained between 3.3 and 6.2 mg/dl.

Osteomalacia in a patient with severe anorexia nervosa.

A 27-year-old woman with anorexia nervosa since adolescence was referred to our unit for generalized bone pain most severe at the pelvis and an inability to stand. She reported a pelvic fracture diagnosed one year earlier, which had failed to heal. Laboratory tests showed low serum phosphate, normal total serum calcium corrected for serum albumin, and very low urinary calcium excretion. Serum bone alkaline phosphatase and parathyroid hormone levels were elevated, whereas 25-hydroxy-vitamin D was severely decreased. Multiple vertebral and rib fractures were seen on plain radiographs. Radiographic images consistent with osteomalacia were pseudofractures of the left inferior pubic ramus, a bilateral complete fracture of the superior pubic ramus, and a characteristic pseudofracture (Looser zone) in the lateral margin of the right scapula. Vitamin D-deficient osteomalacia with secondary hyperparathyroidism was strongly suspected at this point, but it was decided not to confirm this diagnosis by bone biopsy with histomorphometry and osteoid labeling because of the emotional instability of the patient. Dual-energy X-ray absorptiometry disclosed severe demineralization. After two months on calcium and vitamin D supplements, the bone pain had abated and the patient was able to stand. Serum calcium had increased; serum phosphate, 25-hydroxy-vitamin D, and parathyroid hormone had returned to normal, and the pseudofractures showed evidence of healing. Osteoporosis is a well-known complication of anorexia nervosa. This case shows that osteomalacia can also occur. Vitamin D status should be assessed in patients with long-standing severe anorexia nervosa.

Effect of one year residence in Antarctica on bone mineral metabolism and body composition.

OBJECTIVE: To evaluate the changes of the biochemical parameters of mineral metabolism and to assess the effect of these changes on the bone mass of young healthy men who voluntarily lived in the Antarctic Continent for one year. DESIGN: Lumbar spine and whole body bone mineral density (BMD) were measured pre- and post-campaign (14 months later). Serum and urinary biochemical parameters were measured every two months. Serum levels of calcium, phosphate, total alkaline phosphatase, parathormone (PTH) and 25-hydroxyvitamin D (250HD) were determined in blood fasting samples; and hydroxyproline, calcium and creatinine in 2 h fasting urine. The subjects received a dose of 100 i.u./d of vitamin D during May after obtaining the samples and then an average of 125 i.u./d from July to January. SUBJECTS: Seventeen healthy volunteers, who left Buenos Aires during the 1992 summer: ten arrived in the Belgrano II Base at the end of January and the other seven arrived in San Martín in March and stayed there up to summer 1993. RESULTS: BMD increased in lumbar spine (L2-L4), total body and the subarea of the legs but there were no differences between the pre- and post-campaign values in arms and pelvis. The percentage of fat mass decreased significantly after 1 y of residence in Antarctica, in comparison to the basal values. Most biochemical parameters remained unaltered and within the normal range during the whole study. PTH showed a nadir in March (end of the summer) when compared to initial levels (73.0 +/- 28.2 vs 39.9 +/- 32.7 pg/ml, P < 0.05), and recovered its initial value in spring. Calcium levels showed a significant decrease in March (9.5 +/- 0.4 vs 8.5 +/- 1.0 mg%, P < 0.01). 25OHD levels began to decrease in March (24.7 +/- 6.4 vs 18.7 +/- 5.3 ng/ml), reaching a minimum value whose difference approached statistical significance during the winter period (July: 16.4 +/- 8.2 ml, 0.05 < P < 0.06). No significant changes in serum phosphate, total alkaline phosphatase, urinary hydroxyproline/creatinine and calcium/creatinine ratios were found through the year. CONCLUSIONS: 25OHD levels decreased in autumn and winter (nadir in July) and recovered the initial levels by the end of the campaign. An unexplained marked diminution in PTH and serum calcium was found at the beginning of the campaign. In spite of the low vitamin D levels, bone mass in this group of young healthy men increased, probably because of their intense physical activity.

Vitamin D prophylaxis in children with a single dose of 150000 IU of vitamin D.

OBJECTIVE: To determine the efficacy of a single oral dose of 150,000 IU of vitamin D2 at the beginning of autumn for preventing winter vitamin D deficiency in children in Ushuaia (55 degrees S). DESIGN: The study was prospective. SUBJECTS: 79 children clinically healthy with 8.6 +/- 1.4 y of age (X +/- s.d.). INTERVENTIONS: Fasting serum venous samples and 2 h urine samples were obtained immediately before and 6 w and 5 mon after the vitamin D dose. Parents informed consent was obtained previous to the study. In a subgroup of 30 children serum levels of calcium (sCa), phosphorus (sP), total alkaline phosphatase (TAP), 25 hydroxyvitamin D (25 OHD), parathyroid hormone (PTH) and the urine calcium/creatinine ratio in a 2 h urine sample (UCa/UCreat) were measured. In the whole group sCa and the ratio uCa/ucreat were measured. RESULTS: After 150,000 IU of vitamin D2 administration, serum 25 OHD levels at the end of winter (17.0 +/- 9.4 ng/ml) were similar to those at the beginning of autumn (18.7 +/- 10.7 ng/ml), but significantly higher from those obtained in a previous study without vitamin D (9.8 +/- 3.8 ng/ml, P < 0.001). PTH levels were higher at the end of winter (P < 0.02), but this augmentation was lower than the increment observed without vitamin D. Plasma calcium levels and the urine calcium/creatinine ratio were lower at 5 months after vitamin D2 dose (P < 0.02 and P < 0.05 respectively). In the total group the serum calcium was lower after the fifth month (P < 0.05). The Uca/Ucreat ratio was lower at 6 w and 5 mon (P < 0.05 and P < 0.001). CONCLUSION: A single dose of 150,000 IU of vitamin D maintained appropriate levels of 25 OHD without inducing hypercalcemia nor hypercalciuria, but a winter increment of PTH (smaller than in the group without vitamin D) was not inhibited.

Solar ultraviolet B radiation and photoproduction of vitamin D3 in central and southern areas of Argentina.

The incidence of nutritional rickets in the southern part of Argentina is 8-12 times higher than in the rest of the country. Winter 25(OH)D serum levels in normal population of southern areas are lower than in central and northern areas. To elucidate these differences, we compared the photoconversion of provitamin D3 (7-DHC) to previtamin D3 in two cities: Ushuaia (latitude 55 degrees S) and Buenos Aires (34 degrees S). Ampules containing 7-DHC were exposed to sunlight one day in the middle of each month either from 10:30 a.m. to 2:30 p.m. or from 8:00 a.m. to 5:00 p.m. The percentages of photoproducts formed were determined by high performance liquid chromatography (HPLC). Previous studies have proved that this is a valid model to assess "in vitro" the photoproduction of vitamin D3 in human skin. Previtamin D3 + vitamin D3 formed in Ushuaia were less (p < 0.02) than those found in Buenos Aires during all seasons: summer, (X +/- SEM) 6.4 +/- 0.8% vs. 13.2 +/- 1.8%; autumn, 1.2 +/- 0.7% vs. 6.3 +/- 1.3%; winter, 0.8 +/- 0.7% vs. 3.6 +/- 0.7%; spring, 3.4 +/- 0.5% vs. 9.1 +/- 1.1%. The photoproducts produced from 10:30 a.m. to 2:30 p.m. were similar for each month and latitude to those formed when the ampules were exposed from 8:00 a.m. to 5:00 p.m. We conclude that in Ushuaia there is a prolonged "vitamin D winter" during which cutaneous synthesis of vitamin D is absent, leading to lower serum values of 25(OH)D and contributing to the higher incidence of rickets.

Raquitismo nutricional en la Argentina / Nutritional ricketts in Argentina

Se estudiaron niños sanos con una edad promedio de 7,0 años (rango 4 a 9), a fines del invierno (agosto) en tres cuidades argentinas: Buenos Aires, Ushuaia y Tucumán. Los resultados obtenidos revelan una significativa disminución en los niveles séricos de 25-OH-D en Ushuaia (la ciudad más acestral del mundo), debido a la escasez del número de horas de brillo solar y la diminución de la exposición solar de la piel en duración y superficie. La población depende entonces de la ingesta exógena de vitamina D y de la disponibilidad de los depósitos corporales para compensar el déficit de la síntese endógena. Bajo estas circunstancias, la incidencia del raquitismo en niños es significativamente mayor que en otras regiones del país. Con excepcion de grupos etnicos que residen fuera de su medio original, los niveles de 25-OH-D hallados a fines del invierno en niños sanos de Ushuaia son los más bajos comunicados en la literatura