Cross-Calibration of iDXA and pQCT Scanners at Rural and Urban Research Sites in The Gambia, West Africa.

Between-scanner differences in measures of bone and body composition can obscure or exaggerate physiological differences in multi-site studies or the magnitude of changes in longitudinal studies. We conducted a cross-calibration study at two bone imaging centres in The Gambia, West Africa where DXA (dual-energy X-ray absorptiometry) and pQCT (peripheral Quantitative-Computed Tomography) are routinely used. Repeat scans were obtained from 64 Gambian adults (58% Male) aged Mean(SD) 30.9 (13.5) years with Mean(SD) body mass index (BMI) 21.7 (4.0) kg/m2, using DXA (GE Lunar iDXA, whole body [WB], total hip [TH], lumbar spine [LS]) and pQCT (Stratec XCT2000L/XCT2000, tibia 4%, 50% sites). Between-scanner differences were tested using paired t tests (p < 0.05). Between-scanner correlation was explored with linear regression, and cross-calibration equations derived. Bland-Altman analysis investigated machine trend/bias. When differences were detected (p < 0.05), cross-calibration equations were applied to urban values, with t tests and Bland Altman analysis repeated. Between-scanner differences exceeded the predefined level of statistical significance (p < 0.05) for WB aBMD and BA; all pQCT measures vBMD, BMC, cortical cross-sectional area (CSA) and stress-strain index (SSI). Between-scanner correlation was high (R2:0.92-0.99), except pQCT Mu.Den (R2 = 0.51). Bland Altman plots indicated bias increased with increasing BMD. Cross-calibration equations attenuated all between-scanner differences and systematic bias. Cross-calibration, particularly of pQCT scanners, is an important consideration in multi-site studies particularly where between population comparisons are intended. Our experiences and findings may be generalisable to other resource-limited settings where the logistics of sourcing parts and in-country repair may result in lengthy scanner downtime.

Wearable and Portable GPS Solutions for Monitoring Mobility in Dementia: A Systematic Review.

Dementia is the most common neurodegenerative disorder globally. Disease progression is marked by declining cognitive function accompanied by changes in mobility. Increased sedentary behaviour and, conversely, wandering and becoming lost are common. Global positioning system (GPS) solutions are increasingly used by caregivers to locate missing people with dementia (PwD) but also offer a non-invasive means of monitoring mobility patterns in PwD. We performed a systematic search across five databases to identify papers published since 2000, where wearable or portable GPS was used to monitor mobility in patients with common dementias or mild cognitive impairment (MCI). Disease and GPS-specific vocabulary were searched singly, and then in combination, identifying 3004 papers. Following deduplication, we screened 1972 papers and retained 17 studies after a full-text review. Only 1/17 studies used a wrist-worn GPS solution, while all others were variously located on the patient. We characterised the studies using a conceptual framework, finding marked heterogeneity in the number and complexity of reported GPS-derived mobility outcomes. Duration was the most frequently reported category of mobility reported (15/17), followed by out of home (14/17), and stop and trajectory (both 10/17). Future research would benefit from greater standardisation and harmonisation of reporting which would enable GPS-derived measures of mobility to be incorporated more robustly into clinical trials.

Longitudinal Change in Bone Density, Geometry, and Estimated Bone Strength in Older Men and Women From The Gambia: Findings From the Gambian Bone and Muscle Aging Study (GamBAS).

Musculoskeletal aging in the most resource-limited countries has not been quantified, and longitudinal data are urgently needed to inform policy. The aim of this prospective study was to describe musculoskeletal aging in Gambian adults. A total of 488 participants were recruited stratified by sex and 5-year age band (aged 40 years and older); 386 attended follow-up 1.7 years later. Outcomes were dual-energy X-ray absorptiometry (DXA) (n = 383) total hip areal bone mineral density (aBMD), bone mineral content (BMC), bone area (BA); peripheral quantitative computed tomography (pQCT) diaphyseal and epiphyseal radius and tibia (n = 313) total volumetric BMD (vBMD), trabecular vBMD, estimated bone strength indices (BSIc), cross-sectional area (CSA), BMC, and cortical vBMD. Mean annualized percentage change in bone outcomes was assessed in 10-year age bands and linear trends for age assessed. Bone turnover markers, parathyroid hormone (PTH), and 25-hydroxyvitamin D (25(OH)D) were explored as predictors of change in bone. Bone loss was observed at all sites, with an annual loss of total hip aBMD of 1.2% in women after age 50 years and in men at age 70 years plus. Greater loss in vBMD and BSIc was found at the radius in both men and women; strength was reduced by 4% per year in women and 3% per year in men (p trend 0.02, 0.03, respectively). At cortical sites, reductions in BMC, CSA, and vBMD were observed, being greatest in BMC in women, between 1.4% and 2.0% per annum. Higher CTX and PINP predicted greater loss of trabecular vBMD in women and BMC in men at the radius, and higher 25(OH)D with less loss of tibial trabecular vBMD and CSA in women. The magnitude of bone loss was like those reported in countries where fragility fracture rates are much higher. Given the predicted rise in fracture rates in resource-poor countries such as The Gambia, these data provide important insights into musculoskeletal health in this population. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Machine learning applied to HR-pQCT images improves fracture discrimination provided by DXA and clinical risk factors.

BACKGROUND: Traditional analysis of High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) images results in a multitude of cortical and trabecular parameters which would be potentially cumbersome to interpret for clinicians compared to user-friendly tools utilising clinical parameters. A computer vision approach (by which the entire scan is 'read' by a computer algorithm) to ascertain fracture risk, would be far simpler. We therefore investigated whether a computer vision and machine learning technique could improve upon selected clinical parameters in assessing fracture risk. METHODS: Participants of the Hertfordshire Cohort Study (HCS) attended research visits at which height and weight were measured; fracture history was determined via self-report and vertebral fracture assessment. Bone microarchitecture was assessed via HR-pQCT scans of the non-dominant distal tibia (Scanco XtremeCT), and bone mineral density measurement and lateral vertebral assessment were performed using dual-energy X-ray absorptiometry (DXA) (Lunar Prodigy Advanced). Images were cropped, pre-processed and texture analysis was performed using a three-dimensional local binary pattern method. These image data, together with age, sex, height, weight, BMI, dietary calcium and femoral neck BMD, were used in a random-forest classification algorithm. Receiver operating characteristic (ROC) analysis was used to compare fracture risk identification methods. RESULTS: Overall, 180 males and 165 females were included in this study with a mean age of approximately 76 years and 97 (28 %) participants had sustained a previous fracture. Using clinical risk factors alone resulted in an area under the curve (AUC) of 0.70 (95 % CI: 0.56-0.84), which improved to 0.71 (0.57-0.85) with the addition of DXA-measured BMD. The addition of HR-pQCT image data to the machine learning classifier with clinical risk factors and DXA-measured BMD as inputs led to an improved AUC of 0.90 (0.83-0.96) with a sensitivity of 0.83 and specificity of 0.74. CONCLUSION: These results suggest that using a three-dimensional computer vision method to HR-pQCT scanning may enhance the identification of those at risk of fracture beyond that afforded by clinical risk factors and DXA-measured BMD. This approach has the potential to make the information offered by HR-pQCT more accessible (and therefore) applicable to healthcare professionals in the clinic if the technology becomes more widely available.

Impaired Bone Architecture in Peripubertal Children With HIV, Despite Treatment With Antiretroviral Therapy: A Cross-Sectional Study From Zimbabwe.

HIV infection has multi-system adverse effects in children, including on the growing skeleton. We aimed to determine the association between chronic HIV infection and bone architecture (density, size, strength) in peripubertal children. We conducted a cross-sectional study of children aged 8 to 16 years with HIV (CWH) on antiretroviral therapy (ART) and children without HIV (CWOH) recruited from schools and frequency-matched for age strata and sex. Outcomes, measured by tibial peripheral quantitative computed tomography (pQCT), included 4% trabecular and 38% cortical volumetric bone mineral density (vBMD), 4% and 38% cross-sectional area (CSA), and 38% stress-strain index (SSI). Multivariable linear regression tested associations between HIV status and outcomes, stratified by sex and puberty (Tanner 1-2 versus 3-5), adjusting for age, height, fat mass, physical activity, and socioeconomic and orphanhood statuses. We recruited 303 CWH and 306 CWOH; 50% were female. Although CWH were similar in age to CWOH (overall mean ± SD 12.4 ± 2.5 years), more were prepubertal (ie, Tanner 1; 41% versus 23%). Median age at ART initiation was 4 (IQR 2-7) years, whereas median ART duration was 8 (IQR 6-10) years. CWH were more often stunted (height-for-age Z-score <-2) than those without HIV (33% versus 7%). Both male and female CWH in later puberty had lower trabecular vBMD, CSA (4% and 38%), and SSI than those without HIV, whereas cortical density was similar. Adjustment explained some of these differences; however, deficits in bone size persisted in CWH in later puberty (HIV*puberty interaction p = 0.035 [males; 4% CSA] and p = 0.029 [females; 38% CSA]). Similarly, puberty further worsened the inverse association between HIV and bone strength (SSI) in both males (interaction p = 0.008) and females (interaction p = 0.004). Despite long-term ART, we identified deficits in predicted bone strength in those living with HIV, which were more overt in the later stages of puberty. This is concerning, as this may translate to higher fracture risk later in life. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Sex-specific associations between cardiovascular risk factors and physical function: the Gambian Bone and Muscle Ageing Study.

BACKGROUND: In Sub-Saharan Africa, the prevalence of obesity, cardiovascular disease (CVD) and impaired physical function are increasing due to rapid urbanization. We investigated sex differences in associations between cardiac workload, arterial stiffness, peripheral vascular calcification (PVC) and physical function in Gambian adults. METHODS: A total of 488 Gambians aged 40-75+ years were recruited (men: 239; and women: 249). Supine blood pressure and heart rate were measured to calculate rate pressure product and pulse pressure. Presence of PVC was determined from tibia peripheral quantitative computed tomography scans. Physical function was assessed by chair rise test (CRT), single two-legged jump (s2LJ) and hand grip strength (HGS). Body composition was measured by dual-energy x-ray absorptiometry; body size corrections were used to calculate fat mass index (FMI) and appendicular lean mass index (ALMI). Estimated glomerular filtration rate (eGFR) was measured from fasting blood samples. The relationship between rate pressure product, pulse pressure or presence of PVC (independent variable) with physical function parameters (dependent variable) was tested using linear regression. Sex-interactions were tested (p-int) adjusting for age, eGFR and ALMI/FMI. Results were expressed as mean differences between men and women with 95% confidence intervals. Mediation analyses used ALMI/FMI as mediator. RESULTS: Women weighed less (54.7 kg ± 10.3 vs. 59.9 kg ± 10.3) and were shorter (157.8 cm ± 6.0 vs. 169.2 cm ± 7.0) compared with men (both P < 0.0001). Women had higher FMI (6.8 kg/m2  ± 2.9 vs. 2.9 kg/m2  ± 2.0, P < 0.0001) and eGFR (263.7 mL/min/1.73 m2  ± 133.1 vs. 237.6 mL/min/1.73 m2  ± 134.6), but lower ALMI (6.2 kg/m2  ± 0.7 vs. 8.02 kg/m2  ± 1.0, P < 0.0001) compared with men. There were significant mean differences between men and women in rate pressure product and s2LJ power (-1.08 [-1.21, -0.95]) and force (-0.57 [-0.63, -0.51]), only after adjusting for age, eGFR and FMI. There were significant mean differences in the associations between pulse pressure and CRT power (-0.28 [-0.31, -0.25]), s2LJ power (-1.07 [-1.20, -0.93]) and HGS (-11.94 [-13.35, -10.54]); these differences were greater after adjusting for age, eGFR and FMI, than ALMI. There were similar differences in the associations between PVC and physical function parameters. In men, FMI mediated the association between rate pressuree product and CRT power (P = 0.002), s2LJ force (P < 0.001) and s2LJ power (P = 0.001). ALMI did not mediate associations for either men or women. CONCLUSIONS: Multiple risk factors for CVD were associated with poorer physical function in men and were mediated by FMI. There is a need to identify strategies to slow/prevent the rising CVD burden and poor physical function in Sub-Saharan Africa.

Proactive and Integrated Management and Empowerment in Parkinson's Disease protocol for a randomised controlled trial (PRIME-UK) to evaluate a new model of care.

BACKGROUND: People living with Parkinson's disease experience progressive motor and non-motor symptoms, which negatively impact on health-related quality of life and can lead to an increased risk of hospitalisation. It is increasingly recognised that the current care models are not suitable for the needs of people with parkinsonism whose care needs evolve and change as the disease progresses. This trial aims to evaluate whether a complex and innovative model of integrated care will increase an individual's ability to achieve their personal goals, have a positive impact on health and symptom burden and be more cost-effective when compared with usual care. METHODS: This is a single-centre, randomised controlled trial where people with parkinsonism and their informal caregivers are randomised into one of two groups: either PRIME Parkinson multi-component model of care or usual care. Adults ≥18 years with a diagnosis of parkinsonism, able to provide informed consent or the availability of a close friend or relative to act as a personal consultee if capacity to do so is absent and living in the trial geographical area are eligible. Up to three caregivers per patient can also take part, must be ≥18 years, provide informal, unpaid care and able to give informed consent. The primary outcome measure is goal attainment, as measured using the Bangor Goal Setting Interview. The duration of enrolment is 24 months. The total recruitment target is n=214, and the main analyses will be intention to treat. DISCUSSION: This trial tests whether a novel model of care improves health and disease-related metrics including goal attainment and decreases hospitalisations whilst being more cost-effective than the current usual care. Subject to successful implementation of this intervention within one centre, the PRIME Parkinson model of care could then be evaluated within a cluster-randomised trial at multiple centres.

Parkinson's disease: the nutrition perspective.

Parkinson's disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease and affects about 1% of the population over the age of 60 years in industrialised countries. The aim of this review is to examine nutrition in PD across three domains: dietary intake and the development of PD; whole body metabolism in PD and the effects of PD symptoms and treatment on nutritional status. In most cases, PD is believed to be caused by a combination of genetic and environmental factors and although there has been much research in the area, evidence suggests that poor dietary intake is not a risk factor for the development of PD. The evidence about body weight changes in both the prodromal and symptomatic phases of PD is inconclusive and is confounded by many factors. Malnutrition in PD has been documented as has sarcopaenia, although the prevalence of the latter remains uncertain due to a lack of consensus in the definition of sarcopaenia. PD symptoms, including those which are gastrointestinal and non-gastrointestinal, are known to adversely affect nutritional status. Similarly, PD treatments can cause nausea, vomiting and constipation, all of which can adversely affect nutritional status. Given that the prevalence of PD will increase as the population ages, it is important to understand the interplay between PD, comorbidities and nutritional status. Further research may contribute to the development of interventional strategies to improve symptoms, augment care and importantly, enhance the quality of life for patients living with this complex neurodegenerative disease.

Menopause is associated with bone loss, particularly at the distal radius, in black South African women: Findings from the Study of Women Entering and in Endocrine Transition (SWEET).

Menopause transition is associated with accelerated bone loss, though data are limited from sub-Saharan African (SSA). Our objective was to describe bone density, geometry and estimated strength in women by menopause status and to explore whether patterns differed within those living with HIV. METHODS: Radius and tibia peripheral QCT data were collected for Black South African women (n = 430) aged 40-61 years with verified menopause and HIV status. pQCT outcomes were distal 4 % radius and tibia total cross-sectional area (CSA), total volumetric bone mineral density (vBMD), and compressive bone strength (BSIc); proximal 66 % radius and 38 % tibia cortical vBMD, total CSA, cortical thickness, and Stress-strain Index (SSI). Linear regression assessed associations between pre, peri-, and postmenopausal groups and pQCT outcomes adjusting for age, height, and weight, and then stratified by HIV status. Mean [95%CI] and tests for trend (p-trend) across menopausal groups are presented. RESULTS: Women were mean (SD) age 49.2 (5.3) years, with a body mass index (BMI) of 32.4 (6.3) m/kg2, and 18 % were living with HIV. After adjustment, later menopause stage was associated with lower 4 % radius total mean [95%CIs] vBMD (premenopause: 345.7 [335.8,355.5] vs. postmenopause: 330.1 [322.7,337.6] mg/cm3, p-trend = 0.017) and BSIc (premenopause: 0.39 [0.37,0.41] vs. postmenopause: 0.36 [0.35,0.37] g2/cm4; p-trend = 0.012). Similar trends were observed at the 66 % radius for cortical vBMD (premenopause: 1146.8 [1138.9,1154.6] vs. postmenopause: 1136.1 [1130.1,1142.0] mg/cm3; p-trend = 0.028) and cortical thickness (premenopause: 2.01 [1.95,2.06] vs. postmenopause: 1.93 [1.89,1.98] mm; p-trend = 0.036). After stratification by HIV status a similar patten was observed in women with HIV (cortical vBMD premenopause: 1152.9 [1128.5,1177.2] mg/cm3 vs. postmenopause: 1123.6 [1106.0,1141.2] mg/cm3, p-trend = 0.048). Total CSA varied little by menopause or HIV status at either radius sites; few differences were found at the tibia. CONCLUSION: In black South African women, menopause is associated with lower bone density and strength at the distal radius, a common site of osteoporotic fracture, in addition to lower cortical density and thickness at the proximal radius. Although the sample size was small, following stratification by HIV, women living with HIV had evidence of lower cortical density across menopause stages, unlike those without HIV. These findings raise concern for the incidence of Colles' fractures in postmenopausal women in South Africa; longitudinal studies of fracture incidence and implications of living with HIV are required.

Pregnancy-Related Change in pQCT and Bone Biochemistry in a Population With a Habitually Low Calcium Intake.

In pregnancy, changes in maternal calcium (Ca) economy occur to satisfy fetal Ca demand. It is unclear whether maternal mineral reserves facilitate these requirements and no data exist from sub-Saharan Africa. The aim was to determine skeletal changes with peripheral quantitative computed tomography (pQCT) and bone biochemistry between early second and third trimesters. Pregnant rural Gambians aged 18 to 45 years (n = 467) participating in a trial of antenatal nutritional supplements (ISRCTN49285450) had pQCT scans and blood collections at mean (SD) 14 (3) and 31 (1) weeks' gestation. Outcomes were pQCT: radius/tibia 4% total volumetric bone mineral density (vBMD), trabecular vBMD, total cross-sectional area (CSA), 33%/38% radius/tibia cortical vBMD, bone mineral content (BMC), total CSA; biochemistry: collagen type 1 cross-linked ß-C-telopeptide (ß-CTX), type 1 procollagen N-terminal (P1NP), parathyroid hormone (PTH), and 1,25(OH)2 D. Independent t tests tested whether pooled or within-group changes differed from 0. Multiple regression was performed adjusting for age. Data for change are expressed as mean (confidence interval [CI] 2.5, 97.5%). Radius trabecular vBMD, cortical vBMD, and BMC increased by 1.15 (0.55, 1.75)%, 0.41 (0.24, 0.58)%, and 0.47 (0.25, 0.69)%. Tibia total and trabecular vBMD increased by 0.34 (0.15, 0.54)% and 0.46 (0.17, 0.74)%, while tibia cortical vBMD, BMC, and cortical CSA increased by 0.35 (0.26, 0.44)%, 0.55 (0.41, 0.68)% and 0.20 (0.09, 0.31)%, respectively. CTX, PTH, and 1,25(OH)2 D increased by 23.0 (15.09, 29.29)%, 13.2 (8.44, 19.34)%, and 21.0 (17.67, 24.29)%, while P1NP decreased by 32.4 (-37.19, -28.17)%. No evidence of mobilization was observed in the peripheral skeleton. Resorption, although higher in late versus early gestation, was lower throughout pregnancy compared with non-pregnant non-lactating (NPNL) in the same community. Formation was lower in late pregnancy than in early, and below NPNL levels. This suggests a shift in the ratio of resorption to formation. Despite some evidence of change in bone metabolism, in this population, with habitually low Ca intakes, the peripheral skeleton was not mobilized as a Ca source for the fetus. © 2021 crown copyright . Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). The article published with the permission of the Controller of HMSO and the Queen's Printer of Scotland..

Level and change in bone microarchitectural parameters and their relationship with previous fracture and established bone mineral density loci.

BACKGROUND: Osteoporosis is characterised by a reduction of bone mineral density (BMD) and predisposition to fracture. Bone microarchitecture, measured by high resolution peripheral quantitative computed tomography (HR-pQCT), has been related to fragility fractures and BMD and has been the subject of large-scale genome-wide analysis. We investigated whether fracture was related to baseline values and longitudinal changes in bone microarchitecture and whether bone microarchitecture was associated with established BMD loci. METHODS: 115 males and 99 females (aged 72-81 at baseline) from the Hertfordshire Cohort Study (HCS) were analysed. Fracture history was determined in 2011-2012 by self-report and vertebral fracture assessment. Participants underwent HR-pQCT scans of the distal radius and tibia in 2011-2012 and 2017. Previous fracture in relation to baseline values and changes in tibial HR-pQCT parameters was examined using sex-adjusted logistic regression with and without adjustment for age, sociodemographic, lifestyle and clinical characteristics; baseline values and changes in parameters associated with previous fracture were then examined in relation to four established BMD loci after adjustment for sex and age. RESULTS: Previous fracture was related to: higher trabecular area (fully-adjusted odds ratio [95% CI] per SD greater baseline value: 2.18 [1.27,3.73], p = 0.005); lower total volumetric BMD (0.53 [0.34,0.84], p = 0.007), cortical area (0.53 [0.30,0.95], p = 0.032), cortical BMD (0.56 [0.36,0.88], p = 0.011) and cortical thickness (0.45 [0.27,0.77], p = 0.004); and greater declines in trabecular BMD (p = 0.001). Associations were robust in sex- and fully-adjusted analysis. Relationships between BMD loci and these HR-pQCT parameters were weak: rs3801387 (WNT16) was related to decline in trabecular BMD (p = 0.011) but no other associations were significant (p > 0.05). CONCLUSION: Baseline values of HR-pQCT parameters and greater decline in trabecular BMD were associated with fracture. Change in trabecular BMD was associated with WNT16 which has been demonstrated to influence bone health in murine models and human genome-wide association studies (GWAS).

Pregnancy-Related Bone Mineral and Microarchitecture Changes in Women Aged 30 to 45 Years.

At birth, the neonatal skeleton contains 20 to 30 g calcium (Ca). It is hypothesized maternal bone mineral may be mobilized to support fetal skeletal development, although evidence of pregnancy-induced mineral mobilization is limited. We recruited healthy pregnant (n = 53) and non-pregnant non-lactating (NPNL; n = 37) women aged 30 to 45 years (mean age 35.4 ± 3.8 years) and obtained peripheral quantitative computed tomography (pQCT) and high-resolution pQCT (HR-pQCT) scans from the tibia and radius at 14 to 16 and 34 to 36 weeks of pregnancy, with a similar scan interval for NPNL. Multiple linear regression models were used to assess group differences in change between baseline and follow-up; differences are expressed as standard deviation scores (SDS) ± SEM. Decreases in volumetric bone mineral density (vBMD) outcomes were found in both groups; however, pregnancy-related decreases for pQCT total and trabecular vBMD were -0.65 ± 0.22 SDS and -0.50 ± 0.23 SDS greater (p < .05). HR-pQCT total and cortical vBMD decreased compared with NPNL by -0.49 ± 0.24 SDS and -0.67 ± 0.23 SDS, respectively; trabecular vBMD decreased in both groups to a similar magnitude. Pregnancy-related changes in bone microarchitecture significantly exceeded NPNL change for trabecular number (0.47 ± 0.23 SDS), trabecular separation (-0.54 ± 0.24 SDS), cortical thickness (-1.01 ± 0.21 SDS), and cortical perimeter (0.78 ± 0.23 SDS). At the proximal radius, cortical vBMD and endosteal circumference increased by 0.50 ± 0.23 SDS and 0.46 ± 0.23 SDS, respectively, compared with NPNL, whereas cortical thickness decreased -0.50 ± 0.22 SDS. Pregnancy-related decreases in total and compartment-specific vBMD exceed age-related change at the distal tibia. Changes at the radius were only evident with pQCT at the cortical-rich proximal site and suggest endosteal resorption. Although the magnitude of these pregnancy-related changes in the appendicular skeleton are small, if they reflect global changes across the skeleton at large, they may contribute substantially to the Ca requirements of the fetus. © 2020 Crown copyright. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR). This article is published with the permission of the Controller of HMSO and the Queen's Printer for Scotland.