High prevalence of low bone mineral density but normal trabecular bone score in Norwegian elite Para athletes.

Background: Low bone mineral density (BMD) increases the risk of bone stress injuries (BSI) and is one of several clinical concerns in Para athlete sports medicine. However, whether bone microarchitecture is altered in Para athletes is not known. Objective: We aimed to investigate BMD, bone microarchitecture and incidence of bone stress injuries in Norwegian elite Para athletes. Design: In this cross-sectional study in Para athletes, Dual energy x-ray absorptiometry (iDXA, Lunar, GE Health Care) derived areal BMD, trabecular bone score (TBS), a surrogate marker for bone microarchitecture, and body composition (body weight (BW), lean body mass (LBM), fat mass (FM), fat percentage) were investigated and compared between ambulant and non-ambulant athletes. Also, the association between BMD, TBS and body composition variables was investigated. Incidence of BSI was assessed with a questionnaire and confirmed by a sports physician in a clinical interview. BMD Z-score <-1 was defined as low and ≤-2 as osteoporotic. TBS ≥ 1.31 was normal, 1.23-1.31 intermediate and <1.23 low. Results: Among 38 athletes (26 ± 6 yrs, 14 females), BMD Z-score was low in 19 athletes, and osteoporotic in 11 athletes' lumbar spine (LS) or femoral neck (FN). BMD was lower in non-ambulant vs. ambulant athletes both in LS (1.13 ± 0.19 vs. 1.25 ± 0.14 g/cm2, p = 0.030) and FN (0.90 ± 0.15 vs. 1.07 ± 0.16 g/cm2, p = 0.003). TBS was normal for all athletes. BMD Z-score in LS was positively associated with TBS (r = 0.408, p = 0.013), body weight (r = 0.326, p = 0.046) and lean body mass (r = 0.414, p = 0.010), but not with fat mass or fat percentage. None of the athletes reported any BSI. Conclusions: Half of the Norwegian elite Para athletes had low BMD, and 29% had BMD Z-score <-2 suggesting osteoporosis. Non-ambulant athletes were more prone to low BMD than ambulant athletes. However, despite high prevalence of low BMD, TBS was normal in all athletes, and BSI was absent in this young population.

Positive Effect of Parathyroidectomy Compared to Observation on BMD in a Randomized Controlled Trial of Mild Primary Hyperparathyroidism.

Mild or asymptomatic disease is now the dominating presentation of primary hyperparathyroidism (PHPT). However, bone involvement with decreased bone mineral density (BMD) and an increased risk of fractures has been demonstrated. Indications for parathyroidectomy (PTX) in mild PHPT have been debated for years. There is a need of long-term randomized studies comparing PTX with observation without intervention (OBS). Here, we present bone health data from the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH), a randomized controlled trial, comparing PTX to OBS. This study included 191 patients (96 OBS/95 PTX), and 129 patients (64 OBS/65 PTX) were followed for 10 years to the end of study (EOS). BMD was measured with dual-energy X-ray absorptiometry (DXA), peripheral fractures were noted, and spine radiographs were obtained for vertebral fracture assessment. There was a significant treatment effect of PTX on BMD compared with OBS for all analyzed compartments, most explicit for the lumbar spine (LS) and femoral neck (FN) (p < 0.001). The mean changes in T-score from baseline to 10 years were from 0.41 for radius 33% (Rad33) to 0.58 for LS greater in the PTX group than in the OBS group. There was a significant decrease in BMD for all compartments in the OBS group, most pronounced for FN, Rad33, and ultradistal radius (UDR) (p < 0.001). Even though there was a significant treatment effect of PTX compared with OBS, there was only a significant increase in BMD over time for LS (p < 0.001). We found no difference between groups in fracture frequency in the 10-year cohort, neither with modified intention-to-treat (mITT) analysis nor per protocol analysis. Because BMD is only a surrogate endpoint of bone health and PTX did not reduce fracture risk, observation could be considered a safe option for many patients with mild PHPT regarding bone health in a 10-year perspective. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Mortality and Morbidity in Mild Primary Hyperparathyroidism: Results From a 10-Year Prospective Randomized Controlled Trial of Parathyroidectomy Versus Observation.

BACKGROUND: Primary hyperparathyroidism (PHPT) is a common endocrine disorder associated with increased risk for fractures, cardiovascular disease, kidney disease, and cancer and increased mortality. In mild PHPT with modest hypercalcemia and without known morbidities, parathyroidectomy (PTX) is debated because no long-term randomized trials have been performed. OBJECTIVE: To examine the effect of PTX on mild PHPT with regard to mortality (primary end point) and key morbidities (secondary end point). DESIGN: Prospective randomized controlled trial. (ClinicalTrials.gov: NCT00522028). SETTING: Eight Scandinavian referral centers. PATIENTS: From 1998 to 2005, 191 patients with mild PHPT were included. INTERVENTION: Ninety-five patients were randomly assigned to PTX, and 96 were assigned to observation without intervention (OBS). MEASUREMENTS: Date and causes of death were obtained from the Swedish and Norwegian Cause of Death Registries 10 years after randomization and after an extended observation period lasting until 2018. Morbidity events were prospectively registered annually. RESULTS: After 10 years, 15 patients had died (8 in the PTX group and 7 in the OBS group). Within the extended observation period, 44 deaths occurred, which were evenly distributed between groups (24 in the PTX group and 20 in the OBS group). A total of 101 morbidity events (cardiovascular events, cerebrovascular events, cancer, peripheral fractures, and renal stones) were also similarly distributed between groups (52 in the PTX group and 49 in the OBS group). During the study, a total of 16 vertebral fractures occurred in 14 patients (7 in each group). LIMITATION: During the study period, 23 patients in the PTX group and 27 in the OBS group withdrew. CONCLUSION: Parathyroidectomy does not appear to reduce morbidity or mortality in mild PHPT. Thus, no evidence of adverse effects of observation was seen for at least a decade with respect to mortality, fractures, cancer, cardiovascular and cerebrovascular events, or renal morbidities. PRIMARY FUNDING SOURCE: Swedish government, Norwegian Research Council, and South-Eastern Norway Regional Health Authority.

The Influence of DXA Hardware, Software, Reference Population and Software Analysis Settings on the Bone Mineral Density and T-Score Relationship.

Different dual-energy x-ray absorptiometry (DXA) hardware can affect bone mineral density (BMD) measurements and different reference populations can affect t-scores. Long-term analyses describing differences in the relationship between BMD and t-scores are lacking. BMD-values were plotted against t-scores for 241 Lunar DXA scans on females obtained over 18 years from several centers in Sweden and Norway. The result of the plot was compared to hardware/software versions, reference populations and different software analysis settings (Basic vs Enhanced analysis for total body and Single Photon Absorptiometry (SPA) vs Lunar calibration for forearm). For the forearm compartments, we found different BMD-t-score relationships depending on the use of SPA or Lunar calibration (p<0.001). With Lunar calibration, BMD-values were 24% higher, but there was no effect on t-scores. Total body measurements with iDXA scanners and Enhanced analysis for Prodigy scanners (software version 14.10) resulted in a different BMD-t-score relationship compared to the other hardware/software versions (p<0.001), with the largest discrepancy for lower BMD-values. Switching from Basic to Enhanced analysis generally decreased BMD-values and often changed t-scores (both increased and decreased). For the femoral neck, there were two different BMD-t-score relationships caused by different reference populations (p<0.001). In contrast to total body, the difference for femoral neck was more pronounced for higher values, with little impact in the clinical decision-making area. Hardware, software, reference populations and software analysis settings can affect the BMD-t-score relationship, but do so differently for different compartments. The BMD-t-score-plot is a simple and effective tool to discover systematic differences. Longitudinal analyses of DXA scans should be performed based on raw data analyzed in "one run" with the same software version and settings, in order to avoid systematic differences.

Effects of Parathyroidectomy on Quality of Life: 10 Years of Data From a Prospective Randomized Controlled Trial on Primary Hyperparathyroidism (the SIPH-Study).

Primary hyperparathyroidism (PHPT) was previously considered a disease presenting with multiorgan involvement and a wide range of symptoms. Today, the disease presents with no symptoms or mild symptomatology in most patients. Data regarding nonspecific symptoms such as pain, fatigue, memory loss, depression, and other neuropsychiatric signs have been ambiguous, and results from prospective long-term randomized control trials are lacking. The Scandinavian Investigation on Primary Hyperparathyroidism (SIPH) is a prospective randomized controlled trial (RCT) with 10-year follow up, comparing parathyroidectomy (PTX) to observation without any treatment (OBS). From 1998 to 2005, 191 patients with mild PHPT were included from Sweden, Norway, and Denmark. A total of 95 patients were randomized to PTX and 96 to OBS. The generic Short Form-36 survey (SF-36) and the Comprehensive Psychopathological Rating Scale (CPRS) were studied at baseline, 2, 5, and 10 years after randomization. After 10 years, the PTX group scored significantly better on vitality (PTX 65.1 ± 20.2 versus OBS 57.4 ± 22.7; p = .017) compared to the OBS group in SF-36. We found no differences between the groups in the physical subscales. The OBS group had no significant change in any of the SF-36 scores throughout the study. The CPRS showed an improvement of symptoms in both groups for single items and sum scores after 10 years compared to baseline. There were, however, no significant differences between the two groups in the CPRS data. The results of this large and long-term RCT indicate improvement in some of the mental domains of SF-36 following PTX. However, the treatment effects between the groups were subtle with uncertain clinical significance. The observation group had stable SF-36 values and improvement in CPRS symptom-scores. Thus, in considering only quality of life (QoL) and in the absence of declines in renal and skeletal parameters, it may be safe to observe patients with mild PHPT for a decade. © 2020 American Society for Bone and Mineral Research (ASBMR).

Parathyroid hormone independent hypercalcemia in adults.

Parathyroid independent hypercalcemia is characterized by suppressed parathyroid hormone (PTH) in the presence of hypercalcemia. Well known causes and mechanisms are redistribution of calcium from the skeleton, by malignant diseases; inadequately increased intestinal calcium uptake mediated by increased vitamin D activity, and reduced renal elimination due to medications. Frequent and infrequent causes are discussed, and more recent mechanistic models presented in this review. Most hypercalcemic conditions are stable and in equilibrium between the different organs, whereas the utmost severe cases are characterized by rapid rising calcium levels and renal failure, resulting in a vicious circle where a disequilibrium state is developed. Management and treatment depends on the underlying condition and severity. The aim of this review is to discuss non-parathyroid hypercalcemic conditions as seen in the modern clinic, with a focus on areas where recent gain of knowledge has been achieved.

Severe, reversible dysphagia and malnutrition in a patient with tumour-induced hypophosphataemia.

Up to 20% of hospitalised patients may have low serum phosphate concentrations. In certain groups, such as patients with chronic alcohol overconsumption, severe trauma or sepsis, the prevalence may be 30%-50%. Profound hypophosphataemia is less common, but may lead to severe physiological disturbances. In rare cases, hypophosphataemia is caused by phosphaturic substances excreted from a tumour. Osteomalacia with chronic bone pain and fractures, as well as muscle weakness, is common in such patients. The tumours are often small and difficult to detect. Studies suggest that fibroblast growth factor 23 is a reliable marker for detection of these tumours. Persistent hypophosphatemia unresponsive to supplements should raise clinical alertness. With complete resection of the neoplasm, the symptoms rapidly reverse. If the tumour cannot be removed, treatment relies on supplementation with phosphate and active vitamin D compounds. We present a case report of a patient with severe hypophosphataemia, osteomalacia, dysphagia and malnutrition.