Asociación entre el hiperparatiroidismo secundario a la deficiencia de vitamina D en el embarazo y la frecuencia de preeclampsia / Association between hyperparathyroidism secondary to vitamin D deficiency in pregnancy and the frequency of preeclampsia

Resumen OBJETIVO: Establecer si existe asociación entre el hiperparatiroidismo secundario a una deficiencia de vitamina D en el embarazo y la frecuencia de preeclampsia. MATERIALES Y MÉTODOS: Estudio de casos y controles, prospectivo y longitudinal efectuado en pacientes con y sin preeclampsia que entre el 1 de enero y el 30 de junio del 2021 acudieron al Hospital Universitario de la Universidad Autónoma de Nuevo León para la atención del parto. Criterios de inclusión: pacientes embarazadas con diagnóstico de preeclampsia en el último trimestre de la gestación con tensión arterial igual o mayor a 140-90 mmHg y proteinuria igual o mayor a 30 mg/dL. Para el grupo control: embarazadas sanas, sin diagnóstico de preeclampsia en el último trimestre de la gestación. Criterios de exclusión: tabaquismo, alcoholismo y drogadicción y quienes no aceptaron entrar al estudio o tuvieran diagnóstico de enfermedades médicas crónicas. RESULTADOS: Se estudiaron 90 pacientes divididas en dos grupos: con preeclampsia (n = 45) y sin ésta (control, n = 45). Se encontró una relación entre la deficiencia de vitamina D, la hipocalcemia y la preeclampsia; no así entre la paratohormona y la preeclampsia en los rangos internacionales de la primera. La preeclampsia se encontró con mayor frecuencia en pacientes de 12 a 15 años. CONCLUSIONES: El hiperparatiroidismo secundario a la deficiencia de vitamina D en el embarazo no se observó en pacientes con preeclampsia, quienes sí la padecieron tuvieron concentraciones de paratohormona en límites normales. Se encontró una relación entre la deficiencia de vitamina D, la hipocalcemia y la preeclampsia.

Abstract OBJECTIVE: To establish whether there is an association between hyperparathyroidism secondary to vitamin D deficiency in pregnancy and the frequency of preeclampsia. MATERIALSAND METHODS: Case-control, prospective, longitudinal study performed in patients with and without preeclampsia who between January 1 and June 30, 2021 attended the Hospital Universitario of the Universidad Autónoma de Nuevo Leon for delivery care. Inclusion criteria: pregnant patients with a diagnosis of preeclampsia in the last trimester of gestation with blood pressure equal to or greater than 140-90 mmHg and proteinuria equal to or greater than 30 mg/dL. For the control group: healthy pregnant women without a diagnosis of preeclampsia in the last trimester of gestation. Exclusion criteria: smoking, alcoholism and drug addiction and those who did not agree to enter the study or had a diagnosis of chronic medical diseases. RESULTS: We studied 90 patients divided into two groups: with preeclampsia (n = 45) and without preeclampsia (control, n = 45). A relationship was found between vitamin D deficiency, hypocalcemia, and preeclampsia; a relationship was not found between parathormone and preeclampsia in the international parathormone ranges. Preeclampsia was found more frequently in patients aged 12 to 15 years. CONCLUSIONS: Hyperparathyroidism secondary to vitamin D deficiency in pregnancy was not observed in patients with preeclampsia; those who had it had parathormone concentrations in normal limits. A relationship was found between vitamin D deficiency, hypocalcemia, and preeclampsia.

Effect of Teriparatide or Risedronate in Elderly Patients With a Recent Pertrochanteric Hip Fracture: Final Results of a 78-Week Randomized Clinical Trial.

We present final results of a study comparing teriparatide 20 µg every day (QD) with risedronate 35 mg once per week (QW) started within 2 weeks after surgery for a pertrochanteric hip fracture. Patients with BMD T-score ≤ -2.0 and 25OHD ≥9.2 ng/mL were randomized to receive 26-week double-dummy treatment plus calcium and vitamin D, followed by 52-week open-label treatment with the same assigned active drug. Primary endpoint was change from baseline in lumbar spine (LS) BMD at 78 weeks. Secondary and exploratory endpoints were change in BMD at the proximal femur, function, hip pain (Charnley score and 100 mm Visual Analog Scale [VAS]), quality of life (Short Form-36), radiology outcomes, and safety. Data were analyzed with mixed models for repeated measures (MMRM) and logistic regression. Totally, 224 patients were randomized; 171 (teriparatide: 86) contributed to the efficacy analyses (mean ± SD age: 77 ± 7.7 years, 77% females). Mean baseline LS, femoral neck (FN), and total hip (TH) T-scores were -2.16, -2.63, and -2.51, respectively. At 78 weeks, BMD increased significantly more with teriparatide compared to risedronate at the LS (+11.08% versus +6.45%; p < 0.001) and FN (+1.96% versus -1.19%; p = 0.003), with no significant between-group difference in TH BMD. Timed up-and-go (TUG) test was significantly faster with teriparatide at 6, 12, 18, and 26 weeks (differences: -3.2 to -5.9 s; p = 0.045 for overall difference). Hip pain during TUG test by 100 mm VAS was significantly lower with teriparatide at 18 weeks (adjusted difference: -11.3 mm, p = 0.033; -10.0 and -9.3 mm at 12 and 26 weeks, respectively; p = 0.079 for overall difference). Other secondary and exploratory outcomes were not different. Teriparatide group showed two new hip fractures versus seven with risedronate (p = 0.171) and more frequent hypercalcemia and hyperuricemia. In conclusion, 78-week treatment with teriparatide showed significantly greater increases in LS and FN BMD, less pain, and a faster TUG test versus risedronate. © 2016 American Society for Bone and Mineral Research.

Effects of Teriparatide Compared with Risedronate on Recovery After Pertrochanteric Hip Fracture: Results of a Randomized, Active-Controlled, Double-Blind Clinical Trial at 26 Weeks.

BACKGROUND: Osteoporosis drugs might affect fracture-healing. We therefore studied the effects of teriparatide in comparison with risedronate on recovery after pertrochanteric hip fractures. METHODS: The study was a randomized, multicenter, active-controlled, 78-week trial comparing teriparatide (20 µg/day) with risedronate (35 mg/week) initiated within 2 weeks after fixation of a low-trauma pertrochanteric hip fracture (AO/OTA 31-A1 or 31-A2). The main inclusion criteria were a bone mineral density T-score of ≤-2.0 and 25-OH-vitamin D of ≥9.2 ng/mL. During the first 26 weeks, patients received study medication with oral or injectable placebo plus calcium and vitamin D in a double-blinded fashion. Secondary (Timed Up-and-Go [TUG] test, hip pain, Short Form [SF]-36 health status, and safety) and exploratory (radiographic outcomes and ability to walk) 26-week end points are reported. RESULTS: Of the 224 patients who were randomized, 171 (86 teriparatide, 85 risedronate) were included in the analysis. The mean age was 77 ± 8 years, 77% were female, and 26% had a prior history of low-trauma fracture. The teriparatide group completed the TUG test in a shorter time at 6, 12, 18, and 26 weeks (differences of -5.7, -4.4, -3.1, and -3.1 seconds, respectively; p = 0.021 for the overall difference). They also reported less pain on a visual analog scale immediately after the TUG test at 12 and 18 weeks (adjusted absolute differences of 10.6 and 11.9 mm, respectively; p < 0.05). There were no significant between-group differences in the SF-36 score, Charnley hip pain score, ability to walk, or use of walking aids during follow-up. Radiographic healing at 6, 12, and 26 weeks, mechanical failure of the implant (teriparatide, 7; risedronate, 8), loss of reduction (teriparatide, 2; risedronate, 4), and nonunion (0 cases) were not significantly different. Mild hypercalcemia and hyperuricemia were more frequent with teriparatide. CONCLUSIONS: Teriparatide was associated with less pain and a shorter time to complete the TUG test between 6 and 26 weeks compared with risedronate. Other fracture-recovery outcomes were similar. The results should be interpreted with caution as these were secondary end points. LEVEL OF EVIDENCE: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence.

[Bone mineral density and its association with body composition and metabolic biomarkers of insulin-glucose axis, bone and adipose tissue in women]. / Densidad mineral ósea y su asociación con la composición corporal y biomarcadores metabólicos del eje insulino-glucosa, hueso y tejido adiposo en mujeres.

INTRODUCTION: There are few studies integrating the common causes of osteoporosis and obesity (disorders of body composition). A first step is to investigate correlations between their biological phenotypes to determine their common integrative physiology. OBJECTIVE: To correlate the variation of bone mineral density with phenotypes of body composition and biomarkers of bone physiology, insulin-glucose axis, and adipose tissue. METHODS: Cross-sectional study of 75 women (aged 18-45 years). MEASUREMENTS: Body mass index, waist, fat mass, lean mass (dual-energy X-ray absorptiometry), glucose, insulin, osteocalcin, leptin, tumor necrosis factor alpha. STATISTICAL ANALYSIS: multivariate general linear model, SPSS v.22, p<0.05. RESULTS: Age: 32.08±7.33. Bone mineral content multivariate general linear model 1 with two phenotypes excluded (glucose, insulin): osteocalcin (ß=-0.228, p=0.011), lean mass (ß=0.606, p=0.001) and fat mass (ß=1.237, p=0.001) in 62.0%. The bone mineral density multivariate general linear model 2 with three phenotypes excluded (body mass index, glucose, tumor necrosis factor alpha): insulin (ß=0.250, p=0.024), osteocalcin (ß=-0.362, p=0.001), lean mass (ß=0.512, p=0.001) and fat mass (ß=0.701, p=0.001) in 46.3%. CONCLUSIONS: Results show that body composition with an increased lean mass is beneficial to bone. This study reaffirms the importance of performing regular exercise to prevent muscle loss.

Teriparatide for acceleration of fracture repair in humans: a prospective, randomized, double-blind study of 102 postmenopausal women with distal radial fractures.

Animal experiments show a dramatic improvement in skeletal repair by teriparatide. We tested the hypothesis that recombinant teriparatide, at the 20 microg dose normally used for osteoporosis treatment or higher, would accelerate fracture repair in humans. Postmenopausal women (45 to 85 years of age) who had sustained a dorsally angulated distal radial fracture in need of closed reduction but no surgery were randomly assigned to 8 weeks of once-daily injections of placebo (n = 34) or teriparatide 20 microg (n = 34) or teriparatide 40 microg (n = 34) within 10 days of fracture. Hypotheses were tested sequentially, beginning with the teriparatide 40 microg versus placebo comparison, using a gatekeeping strategy. The estimated median time from fracture to first radiographic evidence of complete cortical bridging in three of four cortices was 9.1, 7.4, and 8.8 weeks for placebo and teriparatide 20 microg and 40 microg, respectively (overall p = .015). There was no significant difference between the teriparatide 40 microg versus placebo groups (p = .523). In post hoc analyses, there was no significant difference between teriparatide 40 microg versus 20 microg (p = .053); however, the time to healing was shorter in teriparatide 20 microg than placebo (p = .006). The primary hypothesis that teriparatide 40 microg would shorten the time to cortical bridging was not supported. The shortened time to healing for teriparatide 20 microg compared with placebo still may suggest that fracture repair can be accelerated by teriparatide, but this result should be interpreted with caution and warrants further study.

Effects of intravenous zoledronic acid once yearly on bone remodeling and bone structure.

UNLABELLED: In a substudy of the HORIZON pivotal fracture trial, in which yearly intravenous zoledronic acid 5 mg was found to significantly reduce risk of various fracture types in patients with postmenopausal osteoporosis, 152 patients underwent bone biopsy. Zoledronic acid reduced bone turnover by 63% and preserved bone structure and volume, with evidence of ongoing bone remodeling in 99% of biopsies obtained. INTRODUCTION: In the HORIZON pivotal fracture trial (PFT), enrolling 7,736 women with postmenopausal osteoporosis, three annual intravenous infusions of the bisphosphonate zoledronic acid (5 mg) significantly reduced morphometric vertebral, clinical vertebral, hip, and nonvertebral fractures by 70%, 77%, 41%, and 25%, respectively. Whereas 79% of patients received zoledronic acid/placebo only (stratum I, n = 6,113), 21% received concomitant treatment with other antiresorptive drugs, excluding other bisphosphonates, PTH, and strontium (stratum II, n = 1,652). MATERIALS AND METHODS: To determine effects on bone remodeling and bone architecture, iliac crest bone biopsies were obtained in 152 patients on active treatment or placebo at 3 yr after double tetracycline labeling. In five patients, only qualitative histology was performed, leaving 147 biopsy cores (79 on active treatment and 68 on placebo) for microCT analysis and histomorphometry. RESULTS: Analysis of bone structure by microCT revealed higher trabecular bone volume (BV/TV) in the zoledronic acid group (median, 16.6% versus 12.8%; p = 0.020). In addition, patients treated with zoledronic acid exhibited higher trabecular numbers (p = 0.008), decreased trabecular separation (p = 0.011), and a trend toward improvement in connectivity density (p = 0.062), all indicating better preservation of trabecular structure after treatment with zoledronic acid. Qualitative analysis revealed presence of tetracycline label in 81 of 82 biopsies from patients on zoledronic acid and all 70 biopsies from placebo patients, indicative of continued bone remodeling. No bone pathology was observed. Zoledronic acid induced a 63% median (71% mean) reduction of the activation frequency (Ac.f; p < 0.0001) and reduced mineralizing surface (MS/BS; p < 0.0001) and volume referent bone formation rate (BFR/BV) versus placebo, indicating reduced bone turnover. Mineral appositional rate was higher in the zoledronic acid group (p = 0.0002), suggesting improved osteoblast function compared with placebo. Mineralization lag time was similar in the two groups, whereas osteoid volume (OV/BV; p < 0.0001) and osteoid thickness (O.Th; p = 0.0094) were lower in zoledronic acid-treated patients, indicating normal osteoid formation and mineralization of newly formed bone. Concomitant administration of other antiresorptive osteoporosis therapies (e.g., raloxifene, tamoxifen, tibolone, ipriflavone) did not significantly alter the tissue level response to zoledronic acid. CONCLUSIONS: Annual dosing for 3 yr with zoledronic acid 5 mg intravenously resulted in a median 63% (mean, 71%) reduction of bone turnover and preservation of bone structure and mass without any signs of adynamic bone. Concomitant treatment with other osteoporosis therapies did not significantly affect the bone response to zoledronic acid.