CGM a promising tool to individualize nutritional strategies in preterm infants: Study

Italy: A recent study published in the European Journal of Pediatrics has shown continuous glucose monitoring (CGM) to be a promising tool for individualizing nutritional strategies in preterm infants during the first weeks of birth.

The study found that macronutrient intakes influence neonatal glucose profile as described by CGM and might contribute to adjusting nutritional intakes in preterm infants.

“Continuous glucose monitoring describes the relationship between the intake of daily parenteral nutrients and time spent in hypo and hyperglycemic ranges,” the researchers reported.

Preterm infants, born before 37 weeks of gestation, often face numerous challenges in adapting to extrauterine life, including the regulation of blood sugar levels or glycemic homeostasis. Adequate nutrition has a pivotal role in supporting their growth and development, with macronutrients such as carbohydrates, proteins, and fats being key components of their diet. Recent advancements in medical technology, particularly CGM, have provided unprecedented insights into the intricate interplay between macronutrient intake and glycemic control in these vulnerable neonates.

As described above, nutritional intake could influence the blood glucose profile during the early life of preterm infants. Alfonso Galderisi from the Institute for Pediatric Research (IRP) in Padua, Veneto, Italy, and colleagues aimed to investigate the impact of macronutrient intake on glycemic homeostasis using continuous glucose monitoring.

For this purpose, the researchers analyzed macronutrient intake in infants born ≤ 32 weeks gestational age (GA) and/or with birth weight ≤ 1500 g. CGM was initiated within 48 hours of birth and maintained for five days.

Mild and severe hypoglycemia were defined as sensor glucose (SG) < 72 mg/dL and <47 mg/dL, respectively, while mild and severe hyperglycemia were SG > 144 mg/dL and >180 mg/dL. Data from 30 participants were included (age 29.9 weeks, birthweight 1230.5 g).

The study led to the following findings:

  • A reduced time in mild hypoglycemia was associated with higher amino acid intake, while increased exposure to hyperglycemia was observed in the presence of higher lipids intake.
  • The birthweight was the strongest predictor of neonatal glucose profile with an inverse relationship between the time spent in hyperglycemia and birthweight.

In conclusion, the study demonstrates the relationship between macronutrient intake and glucose homeostasis during the first days of life of very low birth weight infants wearing a CGM. Higher amino acid intake is associated with reduced time spent in the hypoglycemic range, while greater lipids intake increases exposure to hyperglycemia.

Amino acid and lipid intakes largely impact insulin sensitivity, which in turn, is a major determinant of hyper and hypoglycemia in the first days of birth of preterm infants, explaining this apparent contradiction. Transient glucose fluctuations are mainly due to procedures and the multiple stressors occurring during the first days of life and directly impact insulin sensitivity.

“We hypothesize that amino acid and lipid intakes, in turn, impact glucose fluctuations by directly acting on insulin sensitivity,” the researchers wrote.

Reference:

Guiducci, S., Res, G., Bonadies, L. et al. Impact of macronutrients intake on glycemic homeostasis of preterm infants: evidence from continuous glucose monitoring. Eur J Pediatr (2024). https://doi.org/10.1007/s00431-024-05532-4

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Lower urinary tract symptoms significantly association with anxiety: Study

Lower urinary tract symptoms are significantly associated with anxiety suggests a study published in the Prostate International.

Patients with lower urinary tract symptoms (LUTS) often experience comorbid depression and anxiety, yet the mechanisms underlying this association remain incompletely understood. This prospective study aimed to investigate the relationship between depression, anxiety, and LUTS in men. A prospective study was conducted with 350 male patients who underwent urologic examinations at our institution from January 2021 to December 2021. Of these, 131 patients meeting the inclusion criteria were included. Various questionnaires, including the International Prostate Symptom Score (IPSS) and the Hospital Anxiety and Depression Scale (HADS), as well as LUTS examinations (prostate-specific antigen test, transrectal ultrasonography, and urine flowmetry), were administered.

Results: Among the 350 patients, 131 were included in the analysis, with an average age of 58.0 ± 13.69 years. The total IPSS was 18.0 ± 8.69, with the average voiding symptom score at 8.7 ± 5.19 and the average storage symptom score at 6.0 ± 3.27. Both anxiety and depression were found to be correlated with LUTS (P < 0.05). After adjusting for age, hypertension, and diabetes, anxiety (but not depression) was significantly associated with LUTS based on regression analysis. Men with LUTS are more likely to experience anxiety. Therefore, it is essential to assess and address anxiety when managing men with LUTS.

Reference:

Yu Seob Shin, Kiran Kumar Soni, Dong Yun Lee, Sung Chul Kam. The relationship between depression, anxiety and lower urinary tract symptoms in men, Prostate International, 2024, ISSN 2287-8882, https://doi.org/10.1016/j.prnil.2024.02.002. (https://www.sciencedirect.com/science/article/pii/S2287888224000047)

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Delayed Appendicitis Diagnosis Linked to Increased Hospital Costs, reveals JAMA study

A new study sheds light on the impact of delayed appendicitis diagnosis on hospital care costs, revealing implications for healthcare reimbursement policies and disparities in patient care. Delayed diagnosis of appendicitis is associated with adverse outcomes, prolonged hospital stays, and increased likelihood of readmissions.

Despite evidence of disparities in diagnosis rates, hospitals serving minority populations often receive lower reimbursement, raising concerns about equitable healthcare quality metrics. This study was published in the journal JAMA Network Open. The study was conducted by Kulaskera and colleagues.

Researchers conducted a retrospective cohort study of 76,173 patients aged 18-64 who underwent appendectomy across multiple states in the US. The study analyzed data from 2016 to 2017, focusing on the association between delayed appendicitis diagnosis and hospital care costs. Patients with delayed diagnosis were identified based on prior abdominal diagnoses without appendicitis and no intervention seven days before appendectomy admission.

The key findings of the study were as follows:

  • Patients with delayed diagnosis had 1.23 times increased hospital care costs compared to those without delayed diagnosis.

  • Median unadjusted costs for delayed diagnosis were $11,099, significantly higher than $9177 for non-delayed diagnosis.

  • Adjusted analysis revealed a 1.23 times higher likelihood of increased hospital costs for delayed diagnosis patients.

  • Non-Hispanic Black individuals experienced 1.22 times higher appendicitis hospital care costs compared to non-Hispanic White patients.

  • Older age groups and patients on Medicare disability or Medicaid had significantly greater costs.

The study underscores the importance of timely diagnosis in appendicitis management and its impact on healthcare costs. It highlights disparities in care quality and reimbursement policies, particularly affecting minority populations. Understanding the mechanisms behind delayed diagnosis among minority patients is crucial for addressing healthcare disparities effectively.

Delayed appendicitis diagnosis significantly increases hospital care costs, with implications for healthcare reimbursement policies and disparities in patient care. Addressing disparities in diagnosis rates and implementing equitable quality metrics are essential steps toward improving healthcare outcomes for all populations.

Reference:

Kulasekere, D, Royan, R, Shan Y. Appendicitis Hospitalization Care Costs Among Patients With Delayed Diagnosis of Appendicitis. JAMA Network Open. 2024;7(4):e246721. doi:10.1001/jamanetworkopen.2024.6721.

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Surface pre-reacted glass-ionomer filler containing topical applications may prevent caries: Study

Surface pre-reacted glass-ionomer filler containing topical applications may prevent caries suggests a study published in the Journal of Dentistry.

The objective of this systematic review was to assess the efficacy of topical applications containing surface pre-reacted glass-ionomer filler on dental hard tissues. A comprehensive literature search was conducted in PubMed, MEDLINE, Embase, Scopus, ClinicalTrials.gov, Lilacs and Cochrane Central Register of Controlled Trials (until 15.08.2022). Google and Open Grey were used to search for grey literature and handsearching was conducted. Clinical and in vitro studies conducted on human adult teeth were considered eligible without date and language restrictions. The electronic database generated 2,488 results. In total, 227 studies were found to be relevant from which 71 duplicates were removed. Title and abstract screening were then conducted, and a total of 33 studies met the inclusion criteria were assessed for full text screening. Two authors concluded that 11 studies satisfied the eligibility criteria. In vitro studies were evaluated using an accepted quality assessment tool for dental studies. Cochrane risk of bias tool was used for quality assessment of clinical randomised studies, whilst ROBINS-I tool was used for non-randomised studies. Results: Nine in vitro and only two non-randomised clinical trials were reported to meet the eligibility criteria. Results were grouped and analysed separately according to the study design. Different modes of surface pre-reacted glass-ionomer filler delivery were reported in the included studies. Three studies tested the effect of surface pre-reacted glass-ionomer filler containing toothpastes, whilst three studies investigated the effect of polishing pastes with surface pre-reacted glass-ionomer filler, three studies used eluates as surface pre-reacted glass-ionomer filler delivery method and two studies reported the effect of the coatings. The effect of those vehicles was tested on enamel, dentine or oral biofilm. Each study was analysed individually, and heterogeneity was detected among in vitro and clinical studies. Half of the in vitro studies were medium risk, whilst three were low and two studies presented with high risk. In clinical trials, outcome, confounding, selection biases were reported. Meta-analysis was therefore unable to be carried out. Regardless of the mode of delivery and type of studies, all included studies demonstrated the efficacy of surface pre-reacted glass-ionomer filler containing topical applications to inhibit demineralisation of dental hard tissues at a dose dependant manner. Antimicrobial properties towards cariogenic species were also reported. Surface pre-reacted glass-ionomer filler containing topical applications may serve as potential caries preventive and cariostatic tools.

Reference:

Eleni Dimopoulou, Aylin Baysan. Effect of topical applications containing surface pre-reacted glass-ionomer filler on dental hard tissues-A systematic review, Journal of Dentistry,

2024, 104904, ISSN 0300-5712, https://doi.org/10.1016/j.jdent.2024.104904.

(https://www.sciencedirect.com/science/article/pii/S0300571224000745)

Keywords:

Surface, pre-reacted, glass-ionomer filler, topical applications, prevent, caries, Study, Journal of Dentistry, remineralisation; demineralisation; S-PRG filler; enamel; dentine

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Supplementation with probiotics and vitamin D may benefit cognitive function in schizophrenia patients: Study

Supplementation with probiotics and vitamin D may benefit cognitive function in schizophrenia patients suggests a new study published in the Neuropsychopharmacology Reports.

Manipulation of the intestinal microbiome and supplying vitamin D can attenuate psychiatric symptoms in schizophrenic patients. The current study tried to evaluate the effects of probiotic/vitamin D supplementation on the cognitive function and disease severity of schizophrenic patients. In the present study, 70 patients (aged 18–65) with schizophrenia were recruited. Participants were randomly allocated to the placebo (n = 35) and intervention (probiotic supplements+400 IU vitamin D, n = 35) groups. Severity of disease and cognitive function (primary outcomes) were evaluated by Positive and Negative Syndrome Scale (PANSS) and Montreal Cognitive Assessment (MoCA) tests, respectively. Moreover, lipid profile, body mass index (BMI), gastrointestinal (GI) problems, serum C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were evaluated as secondary outcomes. Results: A total of 69 patients completed the study. The MoCA score was increased by 1.96 units in the probiotic-containing supplement group compared to the placebo (p = 0.004). Also, the percentage of subjects with MoCA score ≥ 26 rose significantly in the intervention group (p = 0.031). Moreover, TC (p = 0.011), FBS (p = 0.009), and CRP (p < 0.001) significantly decreased in the supplement group compared to the placebo. Although the probiotic supplement reduced PANSS score by 2.82 units, the difference between the study groups was not statistically significant (p = 0.247). Co-administration of probiotics and vitamin D has beneficial effects on the improvement of cognitive function in schizophrenic patients.

Reference:

Mohammadi A, Sadighi G, Nazeri Astaneh A, Tajabadi-Ebrahimi M, Dejam T. Co-administration of probiotic and vitamin D significantly improves cognitive function in schizophrenic patients: A double-blinded randomized controlled trial. Neuropsychopharmacol Rep. 2024; 00: 1–10. https://doi.org/10.1002/npr2.12431

Keywords:

Supplementation, probiotics, vitamin D, benefit, cognitive, function, schizophrenia patients, Mohammadi A, Sadighi G, Nazeri Astaneh A, Tajabadi-Ebrahimi M, Dejam T, Neuropsychopharmacology Reports

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Insecticide-Treated mosquito Bed Nets Linked to Reduction in Burkitt Lymphoma Incidence: JAMA

Researchers have found that the large-scale rollout of insecticide-treated bed nets (ITNs) in sub-Saharan Africa during the 2000s is associated with a significant reduction in the incidence of Burkitt lymphoma (BL) among children. According to a systematic review and meta-analysis published in JAMA Network Open by Nora S. this important finding highlights an additional benefit of malaria control programs in the region.

Burkitt lymphoma (BL) is one of the most common childhood cancers in sub-Saharan Africa and has been etiologically linked to malaria. However, limited evidence has been available to demonstrate the impact of malaria interventions on BL incidence. The systematic review and meta-analysis aimed to investigate the potential association between the large-scale rollout of ITNs in sub-Saharan Africa and the incidence of BL in children aged 0 to 15 years.

The study involved a systematic review of epidemiological studies on BL incidence rates in children and adolescents in sub-Saharan African countries where malaria is endemic. Researchers searched the Embase, Global Health, and Medline databases, as well as cancer registry publications, to identify studies published between January 1, 1990, and February 27, 2023. The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline.

Data were extracted independently by two reviewers, and the quality of studies was assessed based on predefined criteria: data collection, case ascertainment, and calculation of person-time at risk. The main outcomes and measures included the incidence rates of BL during childhood and mean ITN use in the population. Data were analyzed using a random-effects negative binomial regression model.

The key findings of the study were:

  • Of the 2,333 studies meeting selection criteria, 23 studies comprising 66 data points on BL incidence were included in the analysis.

  • The studies were based on 5,226 BL cases from locations with large-scale ITN use across 17 countries.

  • The incidence rates of BL were found to be 44% (95% CI, 12%-64%) lower in the period after ITN introduction compared to before.

  • The adjusted pooled incidence rates of BL were 1.36 (95% CI, 0.88-2.10) and 0.76 (95% CI, 0.50-1.16) per 100,000 person-years before and after ITN introduction, respectively.

  • After adjusting for potential confounders, a 1-percentage point increase in mean ITN use in the population in the 10 years prior to BL data collection was associated with a 2% (95% CI, 1%-4%) reduction in BL incidence.

The systematic review and meta-analysis provide evidence that the large-scale rollout of ITNs in the 2000s is associated with a reduction in BL burden among children in sub-Saharan Africa. This study underscores the importance of malaria control programs and their potential to impact broader health outcomes in the region.

Reference:

Schmit, N., Kaur, J., & Aglago, E. K. (2024). Mosquito bed net use and burkitt lymphoma incidence in sub-Saharan Africa: A systematic review and meta-analysis. JAMA Network Open, 7(4), e247351. https://doi.org/10.1001/jamanetworkopen.2024.7351

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Increased mammographic breast density associated with cancer recurrence, suggests study

A new study from the Malmö Diet and Cancer Study revealed significant findings that could transform the way breast cancer survivors are monitored post-treatment. The findings were published in the recent edition of The Breast journal.

Breast cancer remains a major health challenge throughout the globe, with ongoing research focusing on how to better predict and prevent recurrences. This study spanned from 1991 to 2014 and focused at mammographic features such as breast density, tumor appearance and mode of detection, along with tumor size, axillary lymph node involvement and histological grade to understand their impact on recurrence-free survival (RFS).

The study analyzed data from a total of 1,082 women who were treated for invasive breast cancer by discovering that the individuals with higher breast density at the time of diagnosis were more likely to experience cancer recurrence. The findings indicate that women with high breast density are at a increased risk of recurrence with a adjusted hazard ratio of 1.32. This risk almost doubled to an adjusted hazard ratio of 2.12 among women whose breast cancer was initially detected through screening.

The analysis excluded 34 women due to metastatic disease at diagnosis or incomplete data and utilized Cox regression methods to establish these associations by providing a clear picture of how mammographic features can impact breast cancer outcomes. Also, no direct association between the mammographic appearance of the tumor and recurrence was observed.

The study highlighted the importance of these findings to identify the links between mammographic features and breast cancer recurrence can significantly aid in designing patient specific follow-up strategies for survivors which could potentially lead to earlier detection of recurrences.

The outcomes of this research underline the need for personalized surveillance strategies that consider individual mammographic features at diagnosis. Through this process, it may be possible to improve the long-term outcomes for breast cancer survivors for the individuals who were identified at higher risk due to their breast density.

Healthcare professionals and policymakers are hopeful that these insights will lead to more effective follow-up care protocols that can help in reducing the rate of breast cancer recurrence and improve survival rates. Overall, this study is a step forward in the breast cancer management by offering potential to enhance the survivorship care plans based on more personalized data.

Reference:

Lång, K., Sturesdotter, L., Bengtsson, Y., Larsson, A.-M., & Sartor, H. (2024). Mammographic features at primary breast cancer diagnosis in relation to recurrence-free survival. In The Breast (p. 103736). Elsevier BV. https://doi.org/10.1016/j.breast.2024.103736

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Cyproheptadine-prazosin combo can reduce drinking in people with alcohol use disorder

A recent study published in the Addiction journal unveiled promising results for treating severe alcohol use disorder (AUD) using a combination of two medications, prazosin and cyproheptadine. This approach targets the α1b and 5HT2A receptors which demonstrated a significant reduction in alcohol consumption among participants.

This phase 2, double-blind, placebo-controlled study was conducted across 32 addiction treatment centers in France and involved a total of 154 participants who were diagnosed with severe AUD. This diverse group included 108 men and 46 women who were all rigorously selected to partake in this research.

The participants were divided into three groups for the three-month treatment duration. The low-dose group (LDG) received 8 mg of cyproheptadine and 5 mg of prazosin in extended-release form daily, while the high-dose group (HDG) was administered 12 mg of cyproheptadine and 10 mg prazosin daily. The control group received a placebo. The primary objective was to observe the change in total alcohol consumption (TAC) from the outset of the trial to the end of the three months.

The results found that both the LDG and HDG showed a significant decrease in TAC when compared to the placebo group, with the HDG demonstrating the most pronounced reduction. The HDG reduced their daily alcohol intake by an impressive 23.6 grams, while the LDG saw a reduction of 18.4 grams. These results were statistically significant and suggest that increased doses of the medication combination may lead to greater reductions in alcohol consumption. The subgroup of participants with very high-risk drinking levels (over 100 grams per day for men and over 60 grams per day for women) found the HDG to show an even more significant decrease in daily drinking by 29.8 grams.

Both medication doses were reported to be well-tolerated by participants by displaying similar safety profiles which are crucial for the treatment of chronic conditions such as AUD. This favorable safety profile combined with the efficacy of the treatment, marks a major step towards the management of alcohol dependence. Overall, these findings provide hope for the individuals with severe alcohol use disorder and contribute to the understanding of the complex neurobiology of addiction.

Source:

Aubin, H., Berlin, I., Guiraud, J., Bruhwyler, J., Batel, P., Perney, P., Trojak, B., Bendimerad, P., Guillou, M., Bisch, M., Grall‐Bronnec, M., Labarrière, D., Delsart, D., Questel, F., Moirand, R., Bernard, P., Trovero, F., Pham, H. P., Tassin, J., & Puech, A. (2024). Prazosin and cyproheptadine in combination in the treatment of alcohol use disorder: A randomized, double‐blind, placebo‐controlled trial. In Addiction. Wiley. https://doi.org/10.1111/add.16484

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Innovative Gastric Cancer Screening Approach Shows Promising Results in Randomized Controlled Trial

In a groundbreaking randomized controlled trial conducted in
Yurihonjo and Nikaho city, Akita Prefecture, researchers have unveiled a new
approach to gastric cancer (GC) screening that could revolutionize early
detection and treatment outcomes. The study compared the efficacy of two
screening methods, Ba-Endo (barium photofluorography following upper
gastrointestinal endoscopy) and ABC-Endo group (upper gastrointestinal
endoscopy according to serological stratification) and found that gastric
cancers could be better cured by endoscopic resection alone in
the ABC-Endo group.

The study results were published in the journal
Gastrointestinal Endoscopy.

Attempts have been undertaken to create an endoscopic
screening system that integrates serological gastric cancer (GC) risk
stratification, specifically the ABC classification, in conjunction with the
yearly population-based GC screening using barium. The study, spanning five
years and involving 1,206 participants, compared the efficacy of two screening
methods: the Ba-Endo group, which underwent annual barium tests followed by
detailed endoscopic examinations, and the ABC-Endo group.

The participants were carefully randomized using the
minimization method, with sex and age considered as key allocation factors.
Over the course of the study, the Ba-Endo group adhered to annual barium tests,
while the ABC-Endo group underwent esophagogastroduodenoscopy (EGD) at varying
intervals, including Group A (EGD only at entry), Group B (EGD once every 3
years), Group C (EGD once every 2 years), and Group D (EGD every year).


Findings:


  • Results from the trial revealed that both groups exhibited a
    similar overall GC detection rate of 1.9%, with 24 detected GC lesions.

  • The Ba-Endo and ABC-Endo groups demonstrated detection rates
    of 2.0% and 1.8%, respectively, showing no statistically significant
    differences between them (P=1.0).

  • However, a remarkable finding emerged when analyzing the
    efficacy of endoscopic resection in treating the detected GCs.


  • Notably, the study found that the rate of GCs cured by
    endoscopic resection alone was 41.6% in the Ba-Endo group. Surprisingly, the
    ABC-Endo group displayed a significantly higher rate, reaching 90.9% (P=0.02).

  • This groundbreaking outcome suggests that the ABC-Endo
    approach, which tailors endoscopy intervals based on individual risk factors,
    holds substantial promise in identifying and successfully treating GCs through
    less invasive means.


These results could potentially reshape the landscape of
gastric cancer screening programs worldwide. The personalized ABC-Endo strategy
not only demonstrated comparable detection rates to the traditional Ba-Endo
method but also exhibited a clear advantage in terms of successful endoscopic
resection, offering patients a less invasive and more effective treatment
option for early-stage gastric cancers. Further research and validation are
crucial, but the promising outcomes of this trial suggest a step forward in the
ongoing fight against gastric cancer.

Further reading: Kusano C, Gotoda T, Ishikawa H, Suzuki S, Ikehara H, Matsuyama Y. Gastric Cancer Detection Rates using Gastrointestinal Endoscopy with Serological Risk Stratification: A Randomized Controlled Trial. Gastrointest Endosc. Published online January 23, 2024. doi: 10.1016/j.gie.2024.01.022

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Vasomotor symptoms closely associated with low BMD in postmenopausal women

A recent study published in the recent edition of Osteoporosis International journal highlight the relationship between vasomotor symptoms (VMS) and bone health in peri- and postmenopausal women. Vasomotor symptoms includes hot flashes, night sweats and have long been recognized as common and distressing experiences for the women who transition through menopause.

The study was conducted by the team of Panagiotis Anagnostis who systematically reviewed and meta-analyzed the existing evidence to investigate the association of VMS with fracture risk and bone mineral density (BMD). The findings were derived from a comprehensive analysis of twenty studies that involved nearly 50,000 women and provide valuable insights into this previously underexplored area.

The outcomes of this research revealed that while VMS did not significantly increase the risk of fractures in postmenopausal women, they were strongly associated with low BMD which is a key indicator of bone health. Specifically, the women who experienced VMS were found to have a 54% increased likelihood of having low BMD when compared to the individuals without such symptoms. This association was more pronounced in the lumbar spine with a significant decrease in BMD observed.

Importantly, the conclusions of this study remained consistent even after accounting for factors such as the severity of VMS, age and study design. Furthermore, the association between VMS and low BMD persisted when the analysis was limited to the studies that excluded the use of menopausal hormone therapy by indicating the robustness of the findings.

Overall, the findings of this study have significant outcomes for the management of the postmenopausal health in women. While VMS may not directly increase the fracture risk, their association with reduced BMD illuminates the importance of addressing these symptoms early on to reduce the potential long-term effects on bone health.

These studies continue to look deeper into the complex interplay between menopause-related symptoms and the various aspects of women’s health that contribute to the valuable evidence which can guide the clinical practice and improve the quality of life for postmenopausal women. The findings underline the need for holistic approaches to menopausal care that prioritize both symptomatic management and the preservation of bone health.

Source:

Anagnostis, P., Lallas, K., Pappa, A., Avgeris, G., Beta, K., Damakis, D., Fountoukidou, E., Zidrou, M., Lambrinoudaki, I., & Goulis, D. G. (2024). The association of vasomotor symptoms with fracture risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis of observational studies. In Osteoporosis International. Springer Science and Business Media LLC. https://doi.org/10.1007/s00198-024-07075-8

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