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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 -
Current Pharmaceutical Design 2022Some reports have pointed out that calcimimetics agents are effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients,... (Meta-Analysis)
Meta-Analysis
A Systematic Review and Meta-analysis of Efficacy and Safety of Calcimimetic Agents in the Treatment of Secondary Hyperparathyroidism in Patients with Chronic Kidney Disease.
BACKGROUND
Some reports have pointed out that calcimimetics agents are effective in the treatment of secondary hyperparathyroidism (SHPT) in chronic kidney disease (CKD) patients, but there is no detailed description of the advantages and disadvantages of calcimimetics agents of SHPT in CKD patients. We tried to pool the published data to verify the effectiveness of calcimimetics agents and to compare the advantages and disadvantages of cinacalcet compared with control in the treatment of SHPT in CKD patients.
METHODS
We included eligible studies of published papers from January 1st, 2000 to December 31st, 2020 in Medline, Pubmed and Web of science databases, and the data were extracted for this meta-analysis.
RESULTS
Twenty-seven studies were eligible, and all the included studies were randomized controlled trials (RCT) including patients treated with long-term dialysis. The results indicated that calcimimetic agents can reduce the parathyroid hormone (PTH, pg/ml) level (WMD = -178.22, 95% CI: -238.57, -117.86, P < 0.00001), calcium (Ca, mg/dl) level (WMD = -0.71, 95% CI: -0.86, -0.55, P < 0.00001), phosphorus (P, mg/dl) level (WMD = -0.32, 95% CI: -0.55, -0.08, P = 0.008), calcium-phosphorus product level (WMD = -7.73, 95% CI: -9.64, -5.82, P < 0.00001). Calcimimetic agents increased the bone alkaline phosphatase (BSAP, ng/ml) levels and rate of achieving target PTH, and reduced osteocalcin levels and the rate of parathyroidectomy. Calcimimetic agents increased the total adverse events' rate, the rate of hypocalcemia and gastrointestinal side effects (nausea, vomiting, abdominal pain and diarrhea), but there was no significant difference in serious adverse events between the calcimimetic agent group and control group.
CONCLUSION
Calcimimetic agents can reduce the PTH level, Ca level, P level, calcium-phosphorus product level and do not increase serious adverse events.
Topics: Humans; Calcimimetic Agents; Calcium; Naphthalenes; Hyperparathyroidism, Secondary; Parathyroid Hormone; Renal Insufficiency, Chronic; Phosphorus; Randomized Controlled Trials as Topic
PubMed: 36305135
DOI: 10.2174/1381612829666221027110656 -
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 -
Clinical Therapeutics Mar 2024The aging of the population increases the incidence of postmenopausal osteoporosis, which threatens the health of elderly women. Abaloparatide is a synthetic peptide... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
The aging of the population increases the incidence of postmenopausal osteoporosis, which threatens the health of elderly women. Abaloparatide is a synthetic peptide analogue of the human parathyroid hormone-related protein that has recently been approved for the treatment of postmenopausal osteoporosis. Its efficacy and safety have not been systematically evaluated. Therefore, studies on the efficacy and safety of abaloparatide could be of assistance in the clinical medication of postmenopausal osteoporosis. The aim of this study was to evaluate the clinical efficacy and safety of abaloparatide in postmenopausal osteoporosis.
METHODS
PubMed, Cochrane Library, EMBASE, and Web of Science databases were electronically searched from inception to July 6, 2023, for relevant randomized controlled trials. Two review authors independently conducted the study screening, quality assessment (based on the Risk of Bias Assessment Tool recommended in the Cochrane handbook), and data extraction. Outcome measures included bone mineral density (BMD), bone turnover and metabolic markers, incidence of fractures, and adverse events. Data analyses were processed by using Stata SE15.
FINDINGS
Ultimately, 8 randomized controlled trials, involving a total of 3705 postmenopausal women, were included. Meta-analysis showed that abaloparatide administration significantly increased the BMD of the lumbar vertebrae (standardized mean difference [SMD], 1.28 [95% CI, 0.81-1.76); I = 78.5%]), femoral neck (SMD, 0.70 [95% CI, 0.17-1.23; I = 75.7%]), and hip bone (SMD, 0.86 [95% CI, 0.53-1.20; I = 60.4%]) in postmenopausal women compared with the control group. Type I procollagen N-terminal propeptide, a bone formation marker, was also elevated after abaloparatide administration. The incidence of vertebral fracture was lower in the abaloparatide group than in the control group (risk ratio, 0.13; 95% CI, 0.06-0.26; I = 0%). There was no significant difference in the incidence of adverse events between the abaloparatide and the placebo groups (risk ratio, 1.03; 95% CI, 0.99-1.06; I = 0%).
IMPLICATIONS
Abaloparatide has a protective effect on women with postmenopausal osteoporosis. It could reduce their risk for vertebral fracture; increase their BMD of the lumbar spine, femoral neck, and hip; and alleviate symptoms and complications of postmenopausal osteoporosis with considerable safety. Limitations of this study include not searching the gray literature and not performing a subgroup analysis. PROSPERO Registration No.: CRD42022370944.
Topics: Female; Humans; Aged; Osteoporosis, Postmenopausal; Parathyroid Hormone-Related Protein; Spinal Fractures; Bone Density Conservation Agents; Bone Density
PubMed: 38307725
DOI: 10.1016/j.clinthera.2023.12.010 -
The British Journal of Nutrition Nov 2015This systematic review aimed to assess the determinants of the parathyroid hormone (PTH) level response to vitamin D supplementation. We searched Medline, Google Scholar... (Meta-Analysis)
Meta-Analysis Review
This systematic review aimed to assess the determinants of the parathyroid hormone (PTH) level response to vitamin D supplementation. We searched Medline, Google Scholar and the reference lists of previous reviews. All randomised controlled trials (RCT) on vitamin D supplementation that involved apparently healthy human subjects with a report of PTH were selected. Potential studies were screened independently and in duplicate. Results are summarised as mean differences with 95% confidence intervals. Quality assessment, subgroup analysis, meta-analysis and meta-regression analysis were carried out. Thirty-three vitamin D supplementation RCT were included. Vitamin D supplementation significantly raised circulating 25-hydroxyvitamin D (25(OH)D) with significant heterogeneity among studies with a pooled mean difference (PMD) of 15.5 ng/ml (test for heterogeneity: P<0·001 and I 2=97·3%). Vitamin D supplementation significantly reduced PTH level with PMD of -8·0 pg/ml, with significant heterogeneity ((test for heterogeneity: P<0·001) and the I 2 value was 97·3%). In the subgroup analyses, the optimum treatment effect for PTH was observed with Ca doses of 600-1200 mg/d (-22·48 pg/ml), after the duration of a >12-month trial (-18·36 pg/ml), with low baseline 25(OH)D concentration of <20 ng/ml (-16·70 pg/ml) and in those who were overweight and obese (-18·11 pg/ml). Despite the present meta-analysis being hindered by some limitations, it provided some interesting evidence, suggesting that suppression of PTH level needs higher vitamin D intake (75 μg/d) than the current recommendations and longer durations (12 months), which should be taken into account for nutritional recommendations.
Topics: Dietary Supplements; Humans; Obesity; Overweight; Parathyroid Hormone; Randomized Controlled Trials as Topic; Vitamin D
PubMed: 26337807
DOI: 10.1017/S0007114515003189 -
Osteoporosis International : a Journal... Apr 2023Sequential treatment of osteoporosis has been increasingly mentioned in recent years. However, the corresponding systematic review has not been reported. This study aims... (Review)
Review
Sequential treatment of osteoporosis has been increasingly mentioned in recent years. However, the corresponding systematic review has not been reported. This study aims to systematically review and assess all full-text pharmacoeconomic studies of sequential treatment for osteoporosis. A comprehensive literature search was performed using PubMed, EMBASE (Ovid), CNKI, and Wanfang Database to identify original articles, published before June 17, 2022. The quality of included articles was evaluated by the updated Consolidated Health Economic Evaluation Reporting Standards (CHEERS 2022) and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases International Osteoporosis Foundation (ESCEO-IOF). In general, ten articles were included in this review. For the comparison between sequential treatment and bisphosphonate monotherapy, more than 75% of studies demonstrated the sequential treatment was cost-effective or dominant, with the exception of sequential treatment involving teriparatide. When the comparisons occurred between the two sequential treatment groups, the sequential treatments associated with either abaloparatide or romosozumab were cost-effective or dominant compared to the sequential treatment involving teriparatide. Several major key drivers of cost-effectiveness included drug cost, medication persistence and adherence, drug effect on fracture risk, offset effect, time horizon, and baseline fracture risk. The most of studies were identified as high quality in CHEERS (2022) and ESCEO-IOF. The cost-effectiveness of sequential treatment for osteoporosis is influenced by multiple factors. Generally, the sequential treatments involving abaloparatide, romosozumab, denosumab, and bisphosphonates may be considered as the preferred option for osteoporosis with high fracture risk, while the sequential treatment with teriparatide was not a cost-effectiveness strategy. The ESCEO-IOF and CHEER (2022) increase the transparency, comparability, extrapolation, and quality of research, engage patients and the general public in research on health services and policies, and help improve the quality of health technology assessment.
Topics: Humans; Cost-Benefit Analysis; Osteoporosis; Fractures, Bone; Musculoskeletal Diseases; Teriparatide; Diphosphonates; Bone Density Conservation Agents
PubMed: 36527476
DOI: 10.1007/s00198-022-06626-1 -
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 -
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 -
Hemodialysis International.... Oct 2023The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a systematic review and meta-analysis of observational studies.
METHODS
The MEDLINE, EMBASE, and Cochrane Library databases were searched in June 2022 to identify studies that evaluated the risk of denosumab-associated hypocalcemia and changes in bone metabolism, changes in BMD from baseline to post-treatment in patients with ESRD.
FINDINGS
Twelve studies with 348 participants were included. The pooled incidence of hypocalcemia during denosumab treatment was 35.0% (95% confidence interval [CI], 25%-46%; I = 63.6%). There were no significant changes in either the serum calcium or phosphate levels from the baseline to post-treatment period; the mean differences were 0.04 mg/dL (95% CI, -0.12 to 0.20 mg/dL) and -0.39 mg/dL (95% CI, -0.89 to 0.12 mg/dL). We found significant changes in the alkaline phosphatase and parathyroid hormone levels; the standardized mean differences were -2.98 (95% CI, -5.36 to -0.59) and -3.12 (95% CI: -4.94 to -1.29), respectively. Denosumab may increase BMD, with mean differences of 9.10% (95% CI: 4.07%-14.13%) and 9.00% (95% CI: 5.93%-12.07%) for the femoral neck and lumbar spine, respectively.
DISCUSSION
Denosumab increased the BMDs of the lumbar spine and femoral neck in patients with ESRD. The onset of hypocalcemia must be carefully monitored during denosumab administration.
Topics: Humans; Bone Density; Denosumab; Hypocalcemia; Bone Density Conservation Agents; Renal Dialysis; Kidney Failure, Chronic
PubMed: 37264758
DOI: 10.1111/hdi.13098