Alendronate Improves Bone Mineral Density in Children and Adolescents Perinatally Infected With Human Immunodeficiency Virus With Low Bone Mineral Density for Age

Abstract Background Children and adolescents with perinatal human immunodeficiency virus (HIV) infection and with low bone mineral density (BMD) may be at higher risk of osteoporosis and fractures in later life than their uninfected peers. Bisphosphonate therapy has been shown to reduce fractures in adults with osteoporosis, but has not been formally studied in youths living with HIV. Methods Fifty-two children and adolescents (aged 11–24 years) perinatally infected with HIV with low lumbar spine (LS) BMD (Z score < −1.5) were randomized to receive once-weekly alendronate or placebo in a double-blind cross-over study designed to assess the safety and efficacy of 48 and 96 weeks of alendronate in the United States and Brazil. All participants received daily calcium carbonate and vitamin D supplementation and were asked to engage in regular weight-bearing exercise. Safety and efficacy are summarized for the initial 48 weeks of the trial. Results Grade 3 or higher abnormal laboratory values, signs, or symptoms developed in 5 of 32 (16%) participants on alendronate and 2 of 18 (11%) on placebo (P > .99). No cases of jaw osteonecrosis, atrial fibrillation, or nonhealing fractures were reported. Mean increases (95% confidence interval) in LS BMD over 48 weeks were significantly larger on alendronate (20% [14%–25%]) than placebo (7% [5%–9%]) (P < .001). Similar improvements were seen for whole body BMD. Conclusions In this small study in children and adolescents perinatally infected with HIV with low LS BMD, 48 weeks of alendronate was well-tolerated, showed no safety concerns, and significantly improved LS and whole body BMD compared to participants on vitamin D/calcium supplementation and exercise alone. Clinical Trials Registration NCT00921557.

Download Full-text

Decreased Bone Mineral Density with Off-Label Use of Tenofovir in Children and Adolescents Infected with Human Immunodeficiency Virus

The Journal of Pediatrics ◽

10.1016/j.jpeds.2007.12.020 ◽

2008 ◽

Vol 152 (4) ◽

pp. 582-584 ◽

Cited By ~ 89

Author(s):

Julia B. Purdy ◽

Rachel I. Gafni ◽

James C. Reynolds ◽

Steven Zeichner ◽

Rohan Hazra

Keyword(s):

Bone Mineral Density ◽

Human Immunodeficiency Virus ◽

Children And Adolescents ◽

Bone Mineral ◽

Off Label Use ◽

Mineral Density ◽

Off Label ◽

Immunodeficiency Virus ◽

Label Use

Download Full-text

Studying the effect of vitamin D supplementation in human immunodeficiency virus (HIV) patients who have experienced loss of bone mineral density over time

http://isrctn.org/> ◽

10.1186/isrctn08265004 ◽

2012 ◽

Author(s):

Barry Peters

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Human Immunodeficiency Virus ◽

Bone Mineral ◽

Vitamin D Supplementation ◽

Mineral Density ◽

Hiv Patients ◽

Immunodeficiency Virus ◽

Over Time

Download Full-text

Safety and Efficacy of 48 and 96 Weeks of Alendronate in Children and Adolescents With Perinatal Human Immunodeficiency Virus Infection and Low Bone Mineral Density for Age

Clinical Infectious Diseases ◽

10.1093/cid/ciaa861 ◽

2020 ◽

Author(s):

Jane C Lindsey ◽

Denise L Jacobson ◽

Hans M Spiegel ◽

Catherine M Gordon ◽

Rohan Hazra ◽

...

Keyword(s):

Bone Mineral Density ◽

Human Immunodeficiency Virus ◽

Virus Infection ◽

Bone Mineral ◽

Mineral Density ◽

Safety And Efficacy ◽

Low Bone Mineral Density ◽

Perinatal Hiv ◽

Immunodeficiency Virus ◽

Randomized Crossover Study

Abstract No safety concerns were identified in a randomized, crossover study of alendronate/placebo in youth with perinatal HIV infection and low bone mineral density (BMD). BMD improved with 48 weeks of alendronate and continued to improve with an additional 48 weeks of therapy. Gains were largely maintained 48 weeks after stopping alendronate.

Download Full-text

Nutritional factors associated with femoral neck bone mineral density in children and adolescents

BMC Musculoskeletal Disorders ◽

10.1186/s12891-019-2901-9 ◽

2019 ◽

Vol 20 (1) ◽

Cited By ~ 1

Author(s):

Guo-Hau Gou ◽

Feng-Jen Tseng ◽

Sheng-Hao Wang ◽

Pao-Ju Chen ◽

Jia-Fwu Shyu ◽

...

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Femoral Neck ◽

Children And Adolescents ◽

Bone Mineral ◽

Age Group ◽

Mineral Density ◽

Nutrient Intakes ◽

Nutritional Factors ◽

Daily Total

Abstract Background Nutritional factors including vitamin D, magnesium, and fat are known to affect bone mineral accrual. This study aimed to evaluate associations between dietary nutrient intakes (both macronutrients and micronutrients) and bone mineral density (BMD) in children and adolescents. Methods Data for this cross-sectional, population-based study were derived from the National Health and Nutrition Examination Survey (NHANES). Participants aged from 8 to 19 years were included. The primary outcome was femoral neck BMD. Results Multivariate analyses revealed that for participants aged 8 to 11, daily sodium intake was significantly and positively associated with femoral neck BMD (B = 0.9 × 10− 5, p = 0.031); in particular, subgroup analyses by sex found that in male participants aged 8–11, daily total cholesterol intake (B = 5.3 × 10− 5, p = 0.030) and calcium intake (B = − 2.0 × 10− 5, p < 0.05) were significantly associated with femoral neck BMD in a positive and negative manner, respectively, but neither were observed in female participants of this age group. In contrast, daily intakes of vitamin D and magnesium were significantly and positively associated with femoral neck BMD in female participants aged 8–11 (B = 246.8 × 10− 5 and 16.3 × 10− 5, p = 0.017 and 0.033, respectively). For participants aged 16 to 19, daily total fat intake was significantly and negatively associated with femoral neck BMD (B = − 58 × 10− 5, p = 0.048); further stratification by sex found that magnesium and sodium intakes were significantly and positively associated with femoral neck BMD only in females of this age group (B = 26.9 × 10− 5 and 2.1 × 10− 5, respectively; both p < 0.05). However, no significant associations between daily nutrient intakes and femoral neck BMD were identified in participants aged 12–15 before or after subgroup stratification. Conclusion The study found that associations of specific nutrition-related variables with BMD of the femoral neck is dependent upon age and gender.

Download Full-text

Bone mineral density and vitamin D concentration: the challenges in taking care of children and adolescents infected with HIV

The Brazilian Journal of Infectious Diseases ◽

10.1016/j.bjid.2017.03.005 ◽

2017 ◽

Vol 21 (3) ◽

pp. 270-275 ◽

Cited By ~ 1

Author(s):

Fabiana Bononi Carmo ◽

Maria Teresa Terreri ◽

Regina Célia de Menezes Succi ◽

Suenia Vasconcelos Beltrão ◽

Aida de Fátima Tomé Barbosa Gouvea ◽

...

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Children And Adolescents ◽

Bone Mineral ◽

Mineral Density ◽

Taking Care

Download Full-text

Reduced bone mineral density in human immunodeficiency virus-infected individuals: a meta-analysis of its prevalence and risk factors

Osteoporosis International ◽

10.1007/s00198-017-4305-8 ◽

2017 ◽

Vol 29 (3) ◽

pp. 595-613 ◽

Cited By ~ 24

Author(s):

S. S. L. Goh ◽

P. S. M. Lai ◽

A. T. B. Tan ◽

S. Ponnampalavanar

Keyword(s):

Risk Factors ◽

Bone Mineral Density ◽

Human Immunodeficiency Virus ◽

Bone Mineral ◽

Meta Analysis ◽

Mineral Density ◽

Immunodeficiency Virus

Download Full-text

O13 Pregnancy vitamin D supplementation leads to greater offspring bone mineral density at 4 years: the MAVIDOS randomised placebo controlled trial

Rheumatology ◽

10.1093/rheumatology/keaa110.012 ◽

2020 ◽

Vol 59 (Supplement_2) ◽

Author(s):

Elizabeth M Curtis ◽

Rebecca J Moon ◽

Stefania D'Angelo ◽

Sarah R Crozier ◽

Nicholas J Bishop ◽

...

Keyword(s):

Bone Mineral Density ◽

Vitamin D ◽

Bone Mass ◽

Bone Mineral ◽

Controlled Trial ◽

Vitamin D Supplementation ◽

Whole Body ◽

Mineral Density ◽

Double Blind ◽

Randomised Controlled

Abstract Background Observational studies have demonstrated associations between maternal gestational vitamin D status and offspring bone health. We have recently shown, in a randomised controlled trial, that pregnancy vitamin D supplementation leads to improved offspring bone mass at birth amongst winter deliveries (when background 25(OH)-vitamin D levels are lowest). In the present analysis, we aimed to evaluate whether the beneficial effect of pregnancy vitamin D supplementation on neonatal bone mass is sustained into early childhood, with bone indices assessed at age 4 years in a subset of participants of the MAVIDOS trial. Methods Pregnant women were randomised in Southampton, Oxford and Sheffield, in a double-blind design, to 1000 IU/day cholecalciferol or matched placebo from 14 weeks’ gestation to birth. At 4 years of age (Southampton participants only, n = 723 births), offspring assessments included anthropometry, whole-body dual-energy x-ray absorptiometry (DXA) [Hologic Horizon, yielding whole body less head (WBLH) bone mineral content (BMC), bone mineral density (BMD), bone area (BA) and lean mass (LM)], and a maternal questionnaire. Linear regression was used to estimate the mean difference (represented by β) in outcomes between the two randomisation arms, adjusted for sex and age at DXA. Further models were additionally adjusted for gestational age, maternal BMI, and child’s sedentary time. All outcomes were standardised to a standard deviation scale, for ease of comparison. Full ethics and MHRA approvals were granted. Results 564 children attended the 4-year visit; 452 had a useable DXA with minimal movement artefact. Maternal pregnancy vitamin D supplementation led to greater offspring indices of bone mass compared with placebo, irrespective of season. For example, WBLH BMD at age 4 years was greater in the offspring of supplemented mothers [β = 0.18 SD (95%CI: 0.00, 0.35), p = 0.047]; there was also evidence of greater LM in the intervention group [β = 0.15 SD (95%CI: -0.02, 0.31), p = 0.081]. In fully adjusted models associations were consistent for lumbar spine indices and for BA and BMC. In keeping with the offspring findings, maternal vitamin D supplementation led to significantly higher maternal plasma 25(OH)D concentrations in late pregnancy (34 weeks’ gestation): placebo group (median(IQR)): 42.4 nmol/l (23.3, 56.4); vitamin D group: 67.4 nmol/l (56.2, 80.3); p < 0.001. Conclusion This is the first ever demonstration in a large placebo-controlled, double-blind randomised controlled trial that maternal pregnancy vitamin D supplementation leads to improved bone and lean mass in children. Our findings suggest that maternal cholecalciferol supplementation may have lasting benefits for offspring musculoskeletal health and thus represent an important public health message. This work was supported by grants from Versus Arthritis 17702, Medical Research Council (MRC #405050259; #U105960371), Bupa Foundation, NIHR Southampton Biomedical Research Centre (BRC), University of Southampton, and NIHR Oxford BRC, University of Oxford. EC was supported by the Wellcome Trust (#201268/Z/16/Z). Disclosures E.M. Curtis None. R.J. Moon None. S. D'Angelo None. S.R. Crozier None. N.J. Bishop None. S. Gopal- Kothandapani None. S. Kennedy None. A.T. Papageorghiou None. R. Fraser None. S.V. Gandhi None. I. Schoenmakers None. A. Prentice None. H.M. Inskip None. K.M. Godfrey None. K. Javaid None. R. Eastell None. C. Cooper None. N.C. Harvey None.

Download Full-text