Age-associated osteoporosis (AAOP) poses a significant health burden, characterized by increased fracture risk due to declining bone mass and strength. Effective prevention and early treatment... Show moreAge-associated osteoporosis (AAOP) poses a significant health burden, characterized by increased fracture risk due to declining bone mass and strength. Effective prevention and early treatment strategies are crucial to mitigate the disease burden and the associated healthcare costs. Current therapeutic approaches effectively target the individual contributing factors to AAOP. Nonetheless, the management of AAOP is complicated by the multitude of variables that affect its development. Main intrinsic and extrinsic factors contributing to AAOP risk are reviewed here, including mechanical unloading, nutrient deficiency, hormonal disbalance, disrupted metabolism, cognitive decline, inflammation and circadian disruption. Furthermore, it is discussed how these can be targeted for prevention and treatment. Although valuable as individual targets for intervention, the interconnectedness of these risk factors result in a unique etiology for every patient. Acknowledgement of the multifaceted nature of AAOP will enable the development of more effective and sustainable management strategies, based on a holistic, patient-centered approach. Show less
Li, M.H.; Noordam, R.; Winter, E.M.; Meurs, M. van; Bouma, H.R.; Arbous, M.S.; ... ; Kooijman, S. 2023
Purpose: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in... Show morePurpose: Sepsis is one of the leading causes of morbidity and mortality worldwide with approximately 50 million annual cases. There is ongoing debate on the clinical benefit of hydrocortisone in the prevention of death in septic patients. Here we evaluated the association between hydrocortisone treatment and mortality in patients diagnosed with sepsis in a large-scale clinical dataset.Methods: Data from patients between 2008 and 2019 were extracted from the retrospective Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Patients who received hydrocortisone after diagnosis were matched using propensity-score matching with patients who did not, to balance confounding (by indication and contraindication) factors between the groups. 90-day mortality and survivors' length of hospital stay was compared between patients who did or did not receive hydrocortisone.Results: A total of 31,749 septic patients were included in the study (mean age: 67, men: 57.3%, in-hospital mortality: 15.6%). 90-day mortality was higher among the 1802 patients receiving hydrocortisone when compared with the 6348 matched non-users (hazard ratio: 1.35, 95% CI: 1.24-1.47). Hydrocortisone treatment was also associated with increased in-hospital mortality (40.9% vs. 27.6%, p < 0.0001) and prolonged hospital stay in those who survived until discharge (median 12.6 days vs. 10.8 days, p < 0.0001). Stratification for age, gender, ethnicity, occurrence of septic shock, and the need for vasopressor drug administration such as (nor) epinephrine did not reveal sub-population(s) benefiting of hydrocortisone use.Conclusion: Hydrocortisone treatment is associated with increased risk of death as well as prolonged hospital stay in septic patients. Although residual confounding (by indication) cannot be ruled out completely due to the observational nature of the study, the present study suggests clinical implication of hydrocortisone use in patients with sepsis. Show less
Chronic nonbacterial osteomyelitis (CNO) is a rare disease spectrum affecting children and adults. Adult CNO may occur as isolated bone inflammation, or with a broad range of extraskeletal features... Show moreChronic nonbacterial osteomyelitis (CNO) is a rare disease spectrum affecting children and adults. Adult CNO may occur as isolated bone inflammation, or with a broad range of extraskeletal features. CNO pathophysiology, including the key drivers of inflammation, remains largely unknown. For pediatric CNO, a role for pro-inflammatory cytokine dysregulation has been proposed, but studies in adults are scarce. We therefore provide immunological characterization of adult CNO. Cross-sectional study in our referral center including adult CNO patients (n = 172) and healthy controls (n = 65). Inflammation parameters and systemic inflammatory based scores(SIBS, including neutrophil/lymphocyte ratio [NLR] and systemic immune inflammation index [SII]) were compared between groups. Cytokine expression was explored with electrochemiluminescent immunoassays in 33 patients, eight healthy controls and 21 osteoporosis patients. Routine inflammation markers were higher in patients than in controls, but generally remained within reference range. Systemic inflammation was more pronounced in patients with additional vertebral involvement as compared to those osteitis in the anterior chest wall alone, in patients with comorbid pustulosis palmoplantaris or psoriasis, and in patients with strongly rather than moderately increased lesional uptake on nuclear imaging. SII was elevated in CNO patients too, but NLR was not. Cytokine expression was generally nondifferential between patients and both control groups, and patients displayed low absolute concentrations of pro-inflammatory cytokines. In this adult CNO cohort, systemic inflammation was generally subtle, but more pronounced in patients with vertebral lesions, associated skin disease, and strongly increased uptake on nuclear imaging. SII was increased in patients compared to healthy controls. Contrasting pediatric studies, we found no increased expression of the pro-inflammatory cytokines that have been proposed to drive the inflammatory cascade, like interleukin-6, -8, and -17 (IL-6, IL-8, and IL-17), and tumor necrosis a (TNF-a). Further studies are needed to evaluate the use of SII in diagnosis and monitoring of CNO, and elucidate the role of cytokine dysregulation in adult disease.(C) 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. Show less
BackgroundChronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition... Show moreBackgroundChronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans.MethodsA primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring.Results36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2-3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNF & alpha;), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNF & alpha; and were considered the most effective treatments.ConclusionsFollowing from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNF & alpha; are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline. Show less
Schoeb, M.; Avci, T.M.; Winter, E.M.; Appelman-Dijkstra, N.M. 2023
Impact microindentation (IMI) is a technique to assess bone material properties of the cortical bone at the tibia in a transcutaneous, microinvasive, way. IMI is increasingly used in studies... Show moreImpact microindentation (IMI) is a technique to assess bone material properties of the cortical bone at the tibia in a transcutaneous, microinvasive, way. IMI is increasingly used in studies evaluating the contribution of tissue material properties to bone fragility in humans, and is approved for use in the clinic in Europe and the United States. Previous data show that IMI is well tolerated during and immediately after the procedure. The aim of this prospective observational study was to evaluate the longer-term safety and acceptability of an IMI measurement using the handheld OsteoProbe device((R)). Included were patients who were scheduled for a measurement at the Leiden University Medical Center from September 2019 to December 2020 and willing to participate. Patients were asked to review the procedure right after the measurement, and by telephone interviews 1 week and 1 month thereafter. The primary outcome was the 30-day complication rate after the measurement. Included were 106 patients (71 women) with a median age of 59 years (range, 20 to 86 years). Only three minor events were reported by 1-week follow-up, with an overall 30-day event rate of 2.8%. These were a very small hematoma in two patients, and a small bruise in one patient, all of which resolved without medical intervention. No other safety-related concerns were observed, and all 106 patients would undergo the measurement again if needed. The vast majority had no pain at baseline, 1-week and 1-month follow-up (80.2%, 88.4% and 94.3%, respectively). In this first and large longitudinal study we demonstrated that although minimally-invasive, IMI using the OsteoProbe((R)) device at the tibia did not lead to any complications, and was well accepted by patients. Results strongly suggest that IMI can be safely used in studies as well as in the clinic in the hands of an experienced operator. (c) 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research. Show less
Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic bone disease caused by a somatic mutation in the GNAS gene. Currently used bone turnover markers (BTMs) do not... Show moreBackground: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare genetic bone disease caused by a somatic mutation in the GNAS gene. Currently used bone turnover markers (BTMs) do not correlate with the clinical picture and are not useful to predict or monitor therapy success. This study assessed the correlation of RANKL, OPG, RANKL/OPG ratio, IL-6 and sclerostin with the classic BTMs alkaline phosphatase (ALP), procollagen type 1 propeptide (P1NP) and beta crosslaps (CTX), with pain, skeletal burden score (SBS) and response to bisphosphonate or denosumab treatment.Methods: Ninety-six serum samples of adult patients >18 years of age with any subtype of FD/MAS were included from the biobank facility of the Leiden University Medical Center, Center for Bone Quality between 2015 and 2021. Standard laboratory assessments were assessed as part of usual care. The concentrations of potential biomarkers RANKL, OPG, sclerostin, IL-6 were analyzed. Data on FD/MAS subtype, age, pain, treatment history and treatment response were retrieved from the electronic patient files. Baseline characteristics were summarized by descriptive statistics. Correlations of the concentrations of the potential biomarkers with classic bone turnover markers, SBS and pain scores were cross-sectionally assessed by Spearman rank order correlation. Correction for multiple testing was performed by Benjamini and Hochberg False Discovery Rate. A sensitivity analyses was performed by excluding patients with SBS below 15 and patients using antiresorptive medication at the time of blood withdrawal or within the wash-out period. In patients treated with bisphosphonates or denosumab after blood withdrawal, pre-treatment concentrations were compared in patients with and without therapy response by Mann Whitney U test.Results: The median age of the patients was 41.2 (Q1-Q3 25.9-52.2) years, 62.5 % was female. Median SBS was 2.5 (Q1-Q3 0.5-7.8). RANKL level correlated weakly with ALP (Spearman rho 0.309, p = 0.004, n = 84), but not with P1NP or CTX. The RANKL/OPG ratio, OPG, IL-6 and sclerostin did not correlate with ALP, P1NP or CTX. None of the potential biomarkers correlated with SBS or pain. Results of the sensitivity analyses were comparable. Pre-treatment biomarker levels were similar in patients with and without improvement in pain scores following bisphosphonate therapy. Pre-treatment RANKL and sclerostin were comparable between patients with and without improvement in pain scores after denosumab therapy. Pre-treatment IL-6 level and the RANKL/OPG ratio seemed to be higher in patients with response to denosumab (IL-6: median 0.64 (Q1-Q3 0.53-0.74) pg/mL, n = 6, RANKL/OPG: median 0.062 (Q1-Q3 0.016-0.331), n = 5) compared to patients without response (IL-6: median 0.35 (0.20-0.54) pg/mL, n = 5, RANKL/OPG: 0.027 (0.024-0.046), n = 4). Pre-treatment IL-6 correlated with the improvement in maximum pain scores (rho 0.962, p < 0.001, n = 9) and average pain scores (rho 0.895, p = 0.001, n = 9) reported during denosumab therapy.Conclusion: Increased concentrations of RANKL, IL-6, sclerostin and of the RANKL/OPG ratio do not indicate severity of FD/MAS, as no correlation was observed of these potential biomarkers with the classic BTMs and SBS. Biomarker levels did not correlate with pain and had no value in predicting bisphosphonate treatment response. These biomarkers are not superior over the currently used methods of assessing ALP, P1NP and CTX or evaluating SBS to establish disease extent or activity and provide no reliable results.Yet, possibly pre-treatment IL-6 and the RANKL/OPG ratio may have some predictive value for clinical response to denosumab. Therefore, studies investigating disease activity and treatment response should include lesional imaging and patient-reported outcome measures. Show less
Meier, M.E.; Hagelstein-Rotman, M.; Ven, A.C. van de; Geest, I.C.M. van der; Donker, O.; Pichardo, S.E.C.; ... ; Appelman-Dijkstra, N.M. 2022
Background: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a... Show moreBackground: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) may cause pain, impaired ambulation and decreased quality of life (QoL). International guidelines advocate management of FD/MAS in a tertiary multidisciplinary care pathway, but no longitudinal data are available to support this recommendation. This multicenter prospective observational study aimed to evaluate effects of 1 year of treatment in the FD/MAS care pathway in 2 tertiary clinics on QoL and pain, assessed by change in Short Form 36 and Brief Pain Inventory between baseline and follow-up. Patients completing baseline questionnaires < 1 year after intake were classified as new referrals, others as under chronic care. Results: 92 patients were included, 61 females (66%). 22 patients (24%) had monostotic disease, 16 (17%) isolated craniofacial FD, 27 (40%) polyostotic FD and 17 (19%) MAS. 26 were new referrals (28%) and 66 chronic patients (72%). Median age at baseline was 47 years (Q1-Q3 36-56). Skeletal burden correlated with baseline Physical Function (r(s) = - 0.281, p = 0.007). QoL was in all domains lower compared to the general population. New referrals reported clinically important differences (CID) over time in domains Physical Function (mean 67 & PLUSMN; SD24 to 74 & PLUSMN; 21, effect size (ES) 0.31, p = 0.020), Role Physical (39 & PLUSMN; 41 to 53 & PLUSMN; 43, ES 0.35, p = 0.066), Social Functioning (64 & PLUSMN; 24 to 76 & PLUSMN; 23, ES 0.49, p = 0.054), and Health Change (39 & PLUSMN; 19 to 53 & PLUSMN; 24, ES 0.76, p = 0.016), chronic patients in Physical Function (52 & PLUSMN; 46 to 66 & PLUSMN; 43, ES 0.31, p = 0.023) and Emotional Wellbeing (54 & PLUSMN; 27 to 70 & PLUSMN; 15, ES 0.59, p < 0.001). New referrals reported a CID of 1 point in maximum pain, average pain and pain interference, chronic patients reported stable scores. Change in pain interference and Role Physical were correlated (r(s) = - 0.472, p < 0.001). Patients with limited disease extent improved more than patients with severe disease. Patients receiving FD-related therapy had lower baseline scores than patients not receiving therapy and reported improvements in QoL after 1 year. Yet also patients without FD-related therapy improved in Physical Function. Conclusions: All FD-subtypes may induce pain and reduced QoL. A multidisciplinary care pathway for FD/MAS may improve pain and QoL, mainly in new referrals without MAS comorbidities with low baseline scores. Therefore, we recommend referral of patients with all subtypes of FD/MAS to specialized academic centers. Show less
Objectives: Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named sternocostoclavicular... Show moreObjectives: Chronic nonbacterial osteomyelitis (CNO) is a rare inflammatory bone disease. The distinct CNO subtype that affects the anterior chest wall is descriptively named sternocostoclavicular hyperostosis (SCCH) and mainly occurs in adults. Literature on CNO/SCCH is scattered and lacks diagnostic and therapeutic consensus. Methods: Systematic review and meta-analysis aiming to characterize clinical presentation and therapeutic modalities applied in adult CNO/SCCH patients. Untransformed numerical data and double-arcsine transformed proportional data were pooled in a random effects model in R-4.0.5; proportions were reported with 95% CI. Results: Forty studies were included, containing data on 2030 and 642 patients for aim 1 and 2, respectively. A female predisposition (67%, 95% CI 60, 73) and major diagnostic delay (5 years 95% CI 3, 7) were noted. Clinical presentation included chest pain (89%, 95% CI 79, 96) and swelling (79%, 95% CI 62, 91). Patients suffered from pustulosis palmoplantaris (53%, 95% CI 37, 68), arthritis (24%, 95% CI 11, 39) and acne (8%, 95% CI 4, 13). Inflammatory markers were inconsistently elevated. Autoantibody and HLA-B27 prevalence was normal, and histopathology unspecific. Increased isotope uptake (99%, 95% CI 96, 100) was a consistent imaging finding. Among manifold treatments, pamidronate and biologicals yielded good response in 83%, 95% CI 60, 98 and 56%, 95% CI 26, 85, respectively. Conclusion: CNO/SCCH literature proves heterogeneous regarding diagnostics and treatment. Timely diagnosis is challenging and mainly follows from increased isotope uptake on nuclear examination. Biopsies, autoantibodies and HLA status are non-contributory, and biochemical inflammation only variably detected. Based on reported data, bisphosphonates and biologicals seem reasonably effective, but due to limitations in design and heterogeneity between studies the precise magnitude of their effect is uncertain. Fundamentally, international consensus seems imperative to advance clinical care for CNO/SCCH. Show less
Sternocostoclavicular hyperostosis (SCCH), the main clinical manifestation of chronic non-bacterial osteomyelitis (CNO) in adults, is associated with various degrees of chronic pain and restricted... Show moreSternocostoclavicular hyperostosis (SCCH), the main clinical manifestation of chronic non-bacterial osteomyelitis (CNO) in adults, is associated with various degrees of chronic pain and restricted shoulder girdle function. We evaluated the impact of CNO/SCCH on quality of life (QoL) and its determinants in 136 adult patients with this rare auto-inflammatory bone disorder using the Short Form 36, Brief Pain Inventory, Brief Illness Perception, Utrecht Coping List, and Shoulder Rating questionnaires. Data were compared with those of the general Dutch population, patients with chronic pain, fibrous dysplasia, or osteoarthritis. Eighty-six (64%) predominantly female (85%) patients with completed questionnaires were included in the study. Sixty-four (75%) had isolated CNO/SCCH. Mean delay in diagnosis was 3.0 +/- 5.5 (SD) years, 90% had variable pain, and 84% limited shoulder function. Compared to healthy and chronically diseased reference populations, CNO/SCCH patients demonstrated significant impairments in almost all aspects of QoL, maladaptive illness perceptions, and ineffective coping strategies. For patients with >5-year delay in diagnosis, higher pain scores and limited shoulder function were identified as determinants for impaired QoL. Patients with CNO/SCCH reported significant impairments in QoL associated with clinical and psychological determinants. Clinical measures such as shortening delay in diagnosis, effective pain management, and psychosocial interventions targeting these factors should help minimize the negative impact of CNO/SCCH on QoL. Show less
Schoeb, M.; Winter, E.M.; Malgo, F.; Schipper, I.B.; Wal, R.J.P. van der; Papapoulos, S.E.; Appelman-Dijkstra, N.M. 2022
Bone material properties were assessed using impact microindentation in patients with high-energy trauma fractures. Compared to patients with low-energy trauma fractures, bone material strength... Show moreBone material properties were assessed using impact microindentation in patients with high-energy trauma fractures. Compared to patients with low-energy trauma fractures, bone material strength index was significantly higher in patients with high-energy trauma fractures, and did not differ between patients with osteopenia and those with osteoporosis within each trauma group. Introduction Impact microindentation (IMI) is a technique to assess tissue-level properties of bone at the tibia. Bone material strength index (BMSi), measured by IMI, is decreased in patients with low-energy trauma fractures, independently of areal bone mineral density (aBMD), but there is no information about BMSi in patients with high-energy trauma fractures. In the present study, we evaluated tissue-level properties of bone with IMI in patients with high-energy trauma fractures. Methods BMSi was measured 3.0 months (IQR 2.0-5.8) after the fracture in 40 patients with high-energy trauma and 40 age- and gender-matched controls with low-energy trauma fractures using the OsteoProbe (R) device. Results Mean age of high- and low-energy trauma patients was 57.7 +/- 9.1 and 57.2 +/- 7.7 years, respectively (p = 0.78). Fracture types were comparable in high- vs low-energy trauma patients. Lumbar spine (LS)-aBMD, but not femoral neck (FN)-aBMD, was higher in high- than in low-energy trauma patients (LS 0.96 +/- 0.13 vs 0.89 +/- 0.13 g/cm(2), p = 0.02; FN 0.75 +/- 0.09 vs 0.72 +/- 0.09 g/cm(2), p = 0.09). BMSi was significantly higher in high- than in low-energy trauma patients (84.4 +/- 5.0 vs 78.0 +/- 4.6, p = 0.001), also after adjusting for aBMD (p = 0.003). In addition, BMSi did not differ between patients with osteopenia and those with osteoporosis within each trauma group. Conclusion Our data demonstrate that BMSi and LS-aBMD, but not FN-aBMD, are significantly higher in high-energy trauma patients compared to matched controls with similar fractures from low-energy trauma. Further studies of non-osteoporotic patients with high-energy trauma fracture with measurements of BMSi are warranted to determine whether IMI might help in identifying those with reduced bone strength. Show less
Over the last two decades there have been significant de-velopments in the pharmacotherapy of osteoporosis. The thera-peutic arsenal has expanded with monoclonal antibodies which have been... Show moreOver the last two decades there have been significant de-velopments in the pharmacotherapy of osteoporosis. The thera-peutic arsenal has expanded with monoclonal antibodies which have been developed based on discoveries of the molecular mechanisms underlying bone resorption and bone formation. Denosumab, the antibody binding RANKL, inhibits bone resorp-tion, and romosozumab, the antibody binding sclerostin, inhibits bone resorption and stimulates bone formation as well. Both an-tibodies have shown potent anti-fracture efficacy in randomized clinical trials and this review will discuss the preclinical and clinical studies focusing on the effects on bone mass. After discontinuation of these antibodies, bone mineral density quickly returns to baseline and in the case of denosumab, discontinuation can not only induce rebound bone loss, but also the occurrence of vertebral fractures. Therefore, sequential antiresorptive therapy to maintain bone mass gains and anti-fracture efficacy is of utmost importance and will also be discussed in this review. (c) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons. org/licenses/by/4.0/). Show less
This European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and... Show moreThis European expert consensus statement provides recommendations for the diagnosis and management of primary hyperparathyroidism (PHPT), chronic hypoparathyroidism in adults (HypoPT), and parathyroid disorders in relation to pregnancy and lactation. Specified areas of interest and unmet needs identified by experts at the second ESE Educational Program of Parathyroid Disorders in 2019 were discussed during two virtual workshops in 2021 and subsequently developed by working groups with interest in the specified areas. PHPT is a common endocrine disease. However, its differential diagnosis of familial hypocalciuric hypercalcemia (FHH), the definition and clinical course of normocalcemic PHPT, and the optimal management of its recurrence after surgery represents areas of uncertainty requiring clarifications. HypoPT is an orphan disease characterized by low calcium concentrations due to insufficient PTH secretion, most often secondary to neck surgery. Prevention and prediction of surgical injury to the parathyroid glands are essential to limit the disease-related burden. Long-term treatment modalities including the place for PTH replacement therapy and the optimal biochemical monitoring and imaging surveillance for complications to treatment in chronic HypoPT need to be refined. The physiological changes in calcium metabolism occurring during pregnancy and lactation modify the clinical presentation and management of parathyroid disorders in these periods of life. Modern interdisciplinary approaches to PHPT and HypoPT in pregnant and lactating women and their newborn children are proposed. The recommendations on clinical management presented here will serve as background for further educational material aimed at a broader clinical audience and were developed with the focus on endocrinologists in training. Show less
![Denosumab Reduces Lesional Fluoride Skeletal Burden on Na[18F]F PET-CT in Patients With Fibrous Dysplasia/McCune-Albright Syndrome (vol 106, pg e2980, 2021)](/sites/all/modules/custom/islandora_solr_search/images/defaultimg.png?solr_nav%5Bid%5D=225d8f4c7dc1a5c55149&solr_nav%5Bpage%5D=0&solr_nav%5Boffset%5D=13)
