-
The Journal of Clinical Endocrinology... Aug 2023Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by...
CONTEXT
Kenny-Caffey syndrome (KCS) is a rare hereditary disorder characterized by short stature, hypoparathyroidism, and electrolyte disturbances. KCS1 and KCS2 are caused by pathogenic variants in TBCE and FAM111A, respectively. Clinically the phenotypes are difficult to distinguish.
OBJECTIVE
The objective was to determine and expand the phenotypic spectrum of KCS1 and KCS2 in order to anticipate complications that may arise in these disorders.
METHODS
We clinically and genetically analyzed 10 KCS2 patients from 7 families. Because we found unusual phenotypes in our cohort, we performed a systematic review of genetically confirmed KCS cases using PubMed and Scopus. Evaluation by 3 researchers led to the inclusion of 26 papers for KCS1 and 16 for KCS2, totaling 205 patients. Data were extracted following the Cochrane guidelines and assessed by 2 independent researchers.
RESULTS
Several patients in our KCS2 cohort presented with intellectual disability (3/10) and chronic kidney disease (6/10), which are not considered common findings in KCS2. Systematic review of all reported KCS cases showed that the phenotypes of KCS1 and KCS2 overlap for postnatal growth retardation (KCS1: 52/52, KCS2: 23/23), low parathyroid hormone levels (121/121, 16/20), electrolyte disturbances (139/139, 24/27), dental abnormalities (47/50, 15/16), ocular abnormalities (57/60, 22/23), and seizures/spasms (103/115, 13/16). Symptoms more prevalent in KCS1 included intellectual disability (74/80, 5/24), whereas in KCS2 bone cortical thickening (1/18, 16/20) and medullary stenosis (7/46, 27/28) were more common.
CONCLUSION
Our case series established chronic kidney disease as a new feature of KCS2. In the literature, we found substantial overlap in the phenotypic spectra of KCS1 and KCS2, but identified intellectual disability and the abnormal bone phenotype as the most distinguishing features.
Topics: Humans; Intellectual Disability; Hyperostosis, Cortical, Congenital; Phenotype; Electrolytes; Hypoparathyroidism
PubMed: 36916904
DOI: 10.1210/clinem/dgad147 -
Frontiers in Endocrinology 2022Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to... (Meta-Analysis)
Meta-Analysis
PURPOSE
Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis.
METHODS
The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis.
RESULTS
A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24 h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24 h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed sensitivity and subgroup analyses.
CONCLUSION
Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.
Topics: Humans; Bone Density; Calcium; Bone and Bones; Parathyroid Hormone; Osteoporosis; Essential Hypertension; Hyperaldosteronism; Minerals
PubMed: 36387892
DOI: 10.3389/fendo.2022.1027841 -
The Quarterly Journal of Nuclear... Jun 2023Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by an autonomous overproduction of parathyroid hormone (PTH) by a parathyroid gland. Over the... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Primary hyperparathyroidism (pHPT) is a common endocrine disorder caused by an autonomous overproduction of parathyroid hormone (PTH) by a parathyroid gland. Over the last decade, F-choline (FCH) PET has emerged as a highly performant imaging technique for guiding parathyroidectomy. As cure is the goal of surgery, the main aims of this study were to summarize patient-based sensitivity, positive predictive value (PPV), and cure rate of FCH PET guided surgery in the surgical management of pHPT.
EVIDENCE ACQUISITION
We conducted a systematic review and metaanalysis according to the PRISMA Guidelines. A literature search was performed in the PubMed, Web of Science and Cochrane databases, last updated November 2022. Original articles on choline PET in patients with pHPT mentioning patient-based sensitivity, PPV and cure rate were retained. Quality of included studies was assessed using the QUADAS-2 Tool. Patient-based sensitivity, PPV and cure rate were pooled by using a random-effects model.
EVIDENCE SYNTHESIS
Twenty-three studies including 1716 patients were included for quantitative assessment. FCH PET showed a pooled patient-based sensitivity of 93.8% (95% CI: 89.8-96.3) and PPV of 97% (95% CI: 92.8-98.8) in patients with pHPT. Parathyroid surgery was performed in 1129 patients. The pooled cure rate of PET-guided surgery was 92.8% (95% CI: 87.4-96.0). Heterogeneity was shown to be moderate for all effect sizes.
CONCLUSIONS
FCH PET showed a high patient-based sensitivity, PPV and cure rate of PET guided surgery in patients with pHPT.
Topics: Humans; Hyperparathyroidism, Primary; Parathyroid Glands; Choline; Positron-Emission Tomography; Positron Emission Tomography Computed Tomography
PubMed: 36756935
DOI: 10.23736/S1824-4785.23.03512-4 -
Cureus Apr 2023Fracture nonunion remains a great challenge for orthopedic surgeons. Some bone fractures don't heal promptly, resulting in delayed unions and nonunions, and there is a... (Review)
Review
Fracture nonunion remains a great challenge for orthopedic surgeons. Some bone fractures don't heal promptly, resulting in delayed unions and nonunions, and there is a need for an additional surgical procedure. Previous research has shown that teriparatide, a type of synthetic parathyroid hormone, can promote the formation of callus and lead to healing in individuals with delayed or non-healing bone fractures. Limited systematic reviews exist that examine the use of teriparatide in cases of delayed healing or non-healing bone fractures, which have their limitations. In this review, we overcome those limitations by including prospective studies, retrospective studies, case reports, and case series together. A systematic search of the literature was conducted in both PubMed and Google Scholar up to September of the year 2022. The studies included in our research included adult patients (over the age of 16) diagnosed with delayed union or nonunion of any bone in the body (flat bone, long bone, short bone, or irregular bone). The studies were limited to those written in English. The outcomes that were tracked and recorded include the healing of the fracture and any negative side effects or adverse events. The initial search yielded 504 abstracts and titles. After reviewing these, 32 articles were selected for further analysis, which included 19 case reports, five case series, two retrospective studies, and six prospective studies. Studies included daily (20 micrograms) or weekly (56.5 micrograms) subcutaneous administration of teriparatide. The duration of follow-up for these studies varied from three to 24 months. Based on the available research, it appears that administering teriparatide subcutaneously is a safe treatment option for delayed healing and non-healing bone fractures, with very few to no reported negative side effects. Using teriparatide for induction of callus formation and treating delayed and nonunions is highly safe and effective.
PubMed: 37187628
DOI: 10.7759/cureus.37478 -
The Cochrane Database of Systematic... Mar 2023Primary hyperparathyroidism (PHPT), a disorder in which the parathyroid glands produce excessive amounts of parathyroid hormone, is most common in older adults and... (Review)
Review
BACKGROUND
Primary hyperparathyroidism (PHPT), a disorder in which the parathyroid glands produce excessive amounts of parathyroid hormone, is most common in older adults and postmenopausal women. While most people with PHPT are asymptomatic at diagnosis, symptomatic disease can lead to hypercalcaemia, osteoporosis, renal stones, cardiovascular abnormalities and reduced quality of life. Surgical removal of abnormal parathyroid tissue (parathyroidectomy) is the only established treatment for adults with symptomatic PHPT to prevent exacerbation of symptoms and to be cured of PHPT. However, the benefits and risks of parathyroidectomy compared to simple observation or medical therapy for asymptomatic and mild PHPT are not well established.
OBJECTIVES
To evaluate the benefits and harms of parathyroidectomy in adults with PHPT compared to simple observation or medical therapy.
SEARCH METHODS
We searched CENTRAL, MEDLINE, LILACS, ClinicalTrials.gov and WHO ICTRP from their date of inception until 26 November 2021. We applied no language restrictions.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) comparing parathyroidectomy with simple observation or medical therapy for the treatment of adults with PHPT.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane methods. Our primary outcomes were 1. cure of PHPT, 2. morbidity related to PHPT and 3. serious adverse events. Our secondary outcomes were 1. all-cause mortality, 2. health-related quality of life and 3. hospitalisation for hypercalcaemia, acute renal impairment or pancreatitis. We used GRADE to assess the certainty of the evidence for each outcome.
MAIN RESULTS
We identified eight eligible RCTs that included 447 adults with (mostly asymptomatic) PHPT; 223 participants were randomised to parathyroidectomy. Follow-up duration varied from six months to 24 months. Of the 223 participants (37 men) randomised to surgery, 164 were included in the analyses, of whom 163 were cured at six to 24 months (overall cure rate 99%). Parathyroidectomy compared to observation probably results in a large increase in cure rate at six to 24 months follow-up: 163/164 participants (99.4%) in the parathyroidectomy group and 0/169 participants in the observation or medical therapy group were cured of their PHPT (8 studies, 333 participants; moderate certainty). No studies explicitly reported intervention effects on morbidities related to PHPT, such as osteoporosis, osteopenia, kidney dysfunction, urolithiasis, cognitive dysfunction or cardiovascular disease, although some studies reported surrogate outcomes for osteoporosis and cardiovascular disease. A post-hoc analysis revealed that parathyroidectomy, compared to observation or medical therapy, may have little or no effect after one to two years on bone mineral density (BMD) at the lumbar spine (mean difference (MD) 0.03 g/cm,95% CI -0.05 to 0.12; 5 studies, 287 participants; very low certainty). Similarly, compared to observation, parathyroidectomy may have little or no effect on femoral neck BMD after one to two years (MD -0.01 g/cm, 95% CI -0.13 to 0.11; 3 studies, 216 participants; very low certainty). However, the evidence is very uncertain for both BMD outcomes. Furthermore, the evidence is very uncertain about the effect of parathyroidectomy on improving left ventricular ejection fraction (MD -2.38%, 95% CI -4.77 to 0.01; 3 studies, 121 participants; very low certainty). Four studies reported serious adverse events. Three of these reported zero events in both the intervention and control groups; consequently, we were unable to include data from these three studies in the pooled analysis. The evidence suggests that parathyroidectomy compared to observation may have little or no effect on serious adverse events (RR 3.35, 95% CI 0.14 to 78.60; 4 studies, 168 participants; low certainty). Only two studies reported all-cause mortality. One study could not be included in the pooled analysis as zero events were observed in both the intervention and control groups. Parathyroidectomy compared to observation may have little or no effect on all-cause mortality, but the evidence is very uncertain (RR 2.11, 95% CI 0.20 to 22.60; 2 studies, 133 participants; very low certainty). Three studies measured health-related quality of life using the 36-Item Short Form Health Survey (SF-36) and reported inconsistent differences in scores for different domains of the questionnaire between parathyroidectomy and observation. Six studies reported hospitalisations for the correction of hypercalcaemia. Two studies reported zero events in both the intervention and control groups and could not be included in the pooled analysis. Parathyroidectomy, compared to observation, may have little or no effect on hospitalisation for hypercalcaemia (RR 0.91, 95% CI 0.20 to 4.25; 6 studies, 287 participants; low certainty). There were no reported hospitalisations for renal impairment or pancreatitis.
AUTHORS' CONCLUSIONS
In accordance with the literature, our review findings suggest that parathyroidectomy, compared to simple observation or medical (etidronate) therapy, probably results in a large increase in cure rates of PHPT (with normalisation of serum calcium and parathyroid hormone levels to laboratory reference values). Parathyroidectomy, compared with observation, may have little or no effect on serious adverse events or hospitalisation for hypercalcaemia, and the evidence is very uncertain about the effect of parathyroidectomy on other short-term outcomes, such as BMD, all-cause mortality and quality of life. The high uncertainty of evidence limits the applicability of our findings to clinical practice; indeed, this systematic review provides no new insights with regard to treatment decisions for people with (asymptomatic) PHPT. In addition, the methodological limitations of the included studies, and the characteristics of the study populations (mainly comprising white women with asymptomatic PHPT), warrant caution when extrapolating the results to other populations with PHPT. Large-scale multi-national, multi-ethnic and long-term RCTs are needed to explore the potential short- and long-term benefits of parathyroidectomy compared to non-surgical treatment options with regard to osteoporosis or osteopenia, urolithiasis, hospitalisation for acute kidney injury, cardiovascular disease and quality of life.
Topics: Male; Female; Humans; Aged; Hypercalcemia; Hyperparathyroidism, Primary; Parathyroidectomy; Cardiovascular Diseases; Parathyroid Hormone; Osteoporosis; Randomized Controlled Trials as Topic
PubMed: 36883976
DOI: 10.1002/14651858.CD013035.pub2 -
Orthopedic Research and Reviews 2023Teriparatide is a recombinant human parathyroid hormone analog with anabolic mechanism of action utilized in the treatment of osteoporosis with well-established clinical... (Review)
Review
Teriparatide is a recombinant human parathyroid hormone analog with anabolic mechanism of action utilized in the treatment of osteoporosis with well-established clinical efficacy. Its use is significantly hindered due to label warnings resulting from pre-clinical rat studies demonstrating an increased risk of osteosarcoma. However, clinical trials and post-marketing surveillance studies did not demonstrate any increased risk of osteosarcoma, even after prolonged periods of surveillance reaching up to 15 years, with most of the identified cases of osteosarcomas being solitary and predominantly attributed to other factors. This systematic review provides a comprehensive overview of the currently available literature and provides the highest level of clinical evidence towards demonstrating the lack of any substantial evidence towards osteosarcoma development in patients utilizing TPTD.
PubMed: 37791038
DOI: 10.2147/ORR.S408718 -
Bone Reports Dec 2022To clarify the role of mediators of ectopic mineralization as biomarkers for arterial calcifications. (Review)
Review
AIM
To clarify the role of mediators of ectopic mineralization as biomarkers for arterial calcifications.
METHODS
MEDLINE and Embase were searched for relevant literature, until January 4th 2022. The investigated biomarkers were: calcium, phosphate, parathyroid hormone, vitamin D, pyrophosphate, osteoprotegerin, receptor activator of nuclear factor-kappa B ligand (RANKL), fibroblast growth factor-23 (FGF-23), Klotho, osteopontin, osteocalcin, Matrix Gla protein (MGP) and its inactive forms and vitamin K. Studies solely performed in patients with kidney insufficiency or diabetes mellitus were excluded.
RESULTS
After screening of 8985 articles, a total of 129 articles were included in this systematic review. For all biomarkers included in this review, the results were variable and more than half of the studies for each specific biomarker had a non-significant result. Also, the overall quality of the included studies was low, partly as a result of the mostly cross-sectional study designs. The largest body of evidence is available for phosphate, osteopontin and FGF-23, as a little over half of the studies showed a significant, positive association. Firm statements for these biomarkers cannot be drawn, as the number of studies was limited and hampered by residual confounding or had non-significant results. The associations of the other mediators of ectopic mineralization with arterial calcifications were not clear.
CONCLUSION
Associations between biomarkers of ectopic mineralization and arterial calcification are variable in the published literature. Future longitudinal studies differentiating medial and intimal calcification could add to the knowledge of biomarkers and mechanisms of arterial calcifications.
PubMed: 35769144
DOI: 10.1016/j.bonr.2022.101599 -
Journal of Medicine and Life Nov 2023Dysmenorrhea, affecting approximately 80% of adolescents, significantly impairs quality of life, disrupts sleep patterns, and induces mood changes. Furthermore, its... (Review)
Review
Dysmenorrhea, affecting approximately 80% of adolescents, significantly impairs quality of life, disrupts sleep patterns, and induces mood changes. Furthermore, its economic impact is substantial, accounting for an estimated $200 billion in the United States and $4.2 million in Japan annually. This review aimed to identify the effects of vitamin D and calcium on primary dysmenorrhea. We conducted a comprehensive literature search across Web of Science, PubMed, Scopus, and Science Direct, focusing on studies published from 2010 to 2020. Keywords included 'primary dysmenorrhea', 'vitamin D', '25-OH vitamin D3', 'cholecalciferol', and 'calcium'. The quality assessment of the articles was done using the Consolidated Standards of Reporting Trials (CONSORT) and the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklists, and the risk bias was assessed using the Cochrane assessment tool. Abnormal low Vit. D levels increased the severity of primary dysmenorrhea through increased prostaglandins and decreased calcium absorption. Vitamin D and calcium supplements could reduce the severity of primary dysmenorrhea and the need for analgesics. This systematic review found an inverse relation between the severity of dysmenorrhea and low serum Vit. D and calcium.. Vitamin D and calcium supplements could reduce the severity of primary dysmenorrhea and the need for analgesics.
Topics: Female; Adolescent; Humans; Vitamin D; Calcium; Dysmenorrhea; Quality of Life; Vitamins; Calcifediol; Vitamin D Deficiency; Analgesics; Dietary Supplements
PubMed: 38406773
DOI: 10.25122/jml-2023-0248 -
Frontiers in Endocrinology 2020Currently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Currently, increasing evidence shows that excess aldosterone may have an impact on bone health, and primary aldosteronism (PA) may be a secondary cause of osteoporosis. This problem is worthy of attention because secondary osteoporosis is always potentially reversible, which affects the selection of treatment for PA to some extent. The present systematic review will assess and summarize the available data regarding the relationship between PA and osteoporosis.
METHODS
Pubmed and Embase were searched for clinical trials related to the association between PA and bone metabolism. The results were limited to full-text articles published in English, without restrictions for the publication time. The quality of clinical trials was appraised, and the data were extracted. Biochemical parameters of bone turnover in PA patients were assessed using random-effect meta-analysis. Descriptive analysis was performed for other parameters, for data is insufficient.
RESULTS
A final total of 15 articles were included in this review. The meta-analysis of six studies showed that subjects with PA had higher serum PTH levels (=21.50 pg/ml, 95% CI (15.63, 27.37), <0.00001) and slightly increased urinary calcium levels ( = 1.65 mmol/24 h, 95% CI (1.24, 2.06), < 0.00001) than the EH controls. PA is associated with an increased risk of bone fracture. Bone loss in patients with PA may be reversed by MR antagonists or adrenal surgery.
CONCLUSIONS
PA may be a secondary cause of osteoporosis and is associated with an increased risk of bone fracture. The clarification of the relationships between PA and bone metabolism requires additional prospective randomized controlled studies in a large sample.
Topics: Aldosterone; Bone Density; Bone and Bones; Fractures, Bone; Humans; Hyperaldosteronism; Osteoporosis; Parathyroid Hormone; Spironolactone
PubMed: 33101208
DOI: 10.3389/fendo.2020.574151 -
Journal of Clinical Orthopaedics and... Feb 2020Fracture nonunion remains a great challenge for orthopaedic surgeons. Approximately 5-10% of bone fractures do not heal promptly, and require another surgical procedure.... (Review)
Review
INTRODUCTION
Fracture nonunion remains a great challenge for orthopaedic surgeons. Approximately 5-10% of bone fractures do not heal promptly, and require another surgical procedure. Previously, several small studies have found that teriparatide, a parathyroid hormone (PTH) analogue, has been found to induce union in those with delayed union and nonunion. However, to date, no systematic reviews regarding the use of teriparatide for delayed union and nonunion are available. The present review aims to investigate the safety and efficacy of teriparatide in delayed union and nonunion.
METHODS
Systematic literature search was performed in PubMed, ScienceDirect, and Google Scholar until September 26, 2019. We included studies involving adult patients (age >16 years) diagnosed with delayed union or nonunion fracture regardless of location (long bone, short bone, flat bone or irregular bone). The language was restricted to English and Indonesian. Outcomes that were recorded were fracture union and adverse events.
RESULTS
Initial search found 5416 abstract and titles. Of these, 20 articles consisting of 64 subjects were retrieved. Of these, 15 case reports, 4 case series, and one prospective study were included. All of the studies administered subcutaneous injection of teriparatide 20 μg/day with mean duration of 7.3 ± 1.5 weeks to 9.7 months. Sixty-one (95.3%) of 64 subjects developed complete union. The follow-up ranged from 3 to 24 months. No side effects occurred during the follow-up period.
CONCLUSIONS
Limited evidence demonstrates that daily subcutaneous injection of teriparatide 20 μg is a potential new safe treatment for delayed union and nonunion with no side effects. We highly suggest the use of such drug, as it is highly effective and safe. However, further clinical studies are required to investigate its safety and efficacy.
PubMed: 31992929
DOI: 10.1016/j.jcot.2019.10.009