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.

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).

The effect of surgery on fat mass, lipid and glucose metabolism in mild primary hyperparathyroidism

Context: Mild primary hyperparathyroidism has been associated with increased body fat mass and unfavorable cardiovascular risk factors. Objective: To assess the effect of parathyroidectomy on fat mass, glucose and lipid metabolism. Design, patients, interventions, main outcome measures: 119 patients previously randomized to observation (OBS; n = 58) or parathyroidectomy (PTX; n = 61) within the Scandinavian Investigation of Primary Hyperparathyroidism (SIPH) trial, an open randomized multicenter study, were included. Main outcome measures for this study were the differences in fat mass, markers for lipid and glucose metabolism between OBS and PTX 5 years after randomization. Results: In the OBS group, total cholesterol (Total-C) decreased from mean 5.9 (±1.1) to 5.6 (±1.0) mmol/L (P = 0.037) and LDL cholesterol (LDL-C) decreased from 3.7 (±1.0) to 3.3 (±0.9) mmol/L (P = 0.010). In the PTX group, the Total-C and LDL-C remained unchanged resulting in a significant between-group difference over time (P = 0.013 and P = 0.026, respectively). This difference was driven by patients who started with lipid-lowering medication during the study period (OBS: 5; PTX: 1). There was an increase in trunk fat mass in the OBS group, but no between-group differences over time. Mean 25(OH) vitamin D increased in the PTX group (P < 0.001), but did not change in the OBS group. No difference in parameters of glucose metabolism was detected. Conclusion: In mild PHPT, the measured metabolic and cardiovascular risk factors were not modified by PTX. Observation seems safe and cardiovascular risk reduction should not be regarded as a separate indication for parathyroidectomy based on the results from this study.

Aberrant tryptophan transport in cultured fibroblast from patients with Male Idiopathic Osteoporosis: An in vitro study.

It has been demonstrated, that long-term chronic tryptophan deficiency, results in decreased serotonin synthesis, which may lead to low bone mass and low bone formation. Findings from studies in male patients with idiopathic osteoporosis suggested a decreased transport of tryptophan in erythrocytes of osteoporotic patients, indicating that serotonin system defects may be involved in the etiology of low bone mass. Tryptophan is the precursor of serotonin, and a disturbed transport of tryptophan is implicated in altered serotonin synthesis. However, no study has investigated the tryptophan transport kinetics in MIO patients. The aim of this study is to investigate the kinetic parameters of tryptophan transport in fibroblasts derived from MIO patients compared to age and sex matched controls. Fibroblast cells were cultured from skin biopsies obtained from 14 patients diagnosed with Male Idiopathic Osteoporosis and from 13 healthy age-sex matched controls, without a diagnosis of osteoporosis. Transport of the amino acid tryptophan across the cell membrane was measured by the cluster tray method. The kinetic parameters, maximal transport capacity (Vmax) and affinity constant (Km) were determined by using the Lineweaver-Burke plot equation. The results of this study have shown a significantly lower mean value for Vmax (p = 0.0138) and lower Km mean value (p = 0.0009) of tryptophan transport in fibroblasts of MIO patients compared to the control group. A lower Vmax implied a decreased tryptophan transport availability in MIO patients. In conclusion, reduced cellular tryptophan availability in MIO patients might result in reduced brain serotonin synthesis and its endogenous levels in peripheral tissues, and this may contribute to low bone mass/formation. The findings of the present study could contribute to the etiology of idiopathic osteoporosis and for the development of novel approaches for diagnosis, treatment and management strategies of MIO.

Primary hyperparathyroidism, hypercalciuria, and bone recovery after parathyroidectomy.

BACKGROUND: In primary hyperparathyroidism, successful parathyroidectomy leads to improved bone mineral density in the majority of cases. Our aim was to further explore the relationship between hypercalciuria, kidney function, and bone recovery after parathyroidectomy. METHODS: Bone mineral density, estimated glomerular filtration rate, and 24-hour urinary calcium were analyzed before and one year after parathyroidectomy in a cohort of 150 primary hyperparathyroidism patients (119 women; median age 60 [range 30-80] years) taking part in a clinical trial. The patients were randomized to 1-year daily treatment with either cholecalciferol 1,600 IU and calcium carbonate 1,000 mg or calcium carbonate alone. RESULTS: Baseline 24-hour urinary calcium correlated directly with s-calcium, parathyroid hormone, 25-OH-D, the bone markers beta C-terminal telopeptide of type 1 collagen and procollagen type 1 amino-terminal propeptide, and estimated glomerular filtration rate (r = 0.19-0.30; P < .05) and inversely with age (r = -0.25; P = .004); 24-hour urinary calcium decreased and bone mineral density in lumbar spine and hip increased similarly in the 2 groups. Baseline 24-hour urinary calcium in the highest quartile (>10 mmol/d) was associated with greater increases in all locations. In a multivariable model adjusting for age, sex, smoking, diabetes, body mass index, estimated glomerular filtration rate, baseline bone mineral density, and vitamin D group, the increase in total hip bone mineral density remained independently associated with baseline 24-hour urinary calcium in the highest quartile (>10 mmol/d) and with plasma parathyroid hormone. Patients with persistent increases in 24-hour urinary calcium at follow-up (14%) had similar bone mineral density improvement. CONCLUSION: Overall, 24-hour urinary calcium > 10 mmol/d was an independent determinant of improvement in bone mineral density and should be taken into account when considering parathyroidectomy.

Can secondary osteoporosis be identified when screening for osteoporosis with digital X-ray radiogrammetry? Initial results from the Stockholm Osteoporosis Project (STOP).

OBJECTIVES: To identify causes of low age-adjusted bone mass at digital X-ray radiogrammetry (DXR) in individuals attending an osteoporosis screening program. STUDY DESIGN: In a descriptive observational cohort study, women aged 40-75 years who attended a general mammography screening program had their bone mass investigated with DXR and answered a questionnaire regarding several clinical risk factors for osteoporosis. Each month the 2% with the lowest Z-scores were selected for further clinical examination with DXA of the hip and lumbar spine and pre-defined blood tests. MAIN OUTCOME MEASURE: Causes of secondary osteoporosis determined by clinical and laboratory evaluation. RESULTS: 14,783 women attended mammography screening and had their bone mass evaluated. In total, 327 women had a low DXR BMD and 281 accepted further DXA examination. Of these, 93 (33.1%) had osteoporosis. The diagnosis was new in 79 cases (84.9%) and in 32 (34.4%) a potential underlying cause was identified. Primary hyperparathyroidism was found in 8.6% and secondary hyperparathyroidism in 13.5%. Several self-reported risk factors for osteoporosis, including rheumatic disease, insulin-treated diabetes, cortisone treatment, smoking, reduced mobility, hyperparathyroidism, and malabsorption, were significantly more common among those selected for DXA referral than in the total cohort. For example, rheumatic disease and insulin-treated diabetes were reported 3.4 and 2.3 times as often, respectively. CONCLUSION: The prevailing potential cause of secondary osteoporosis according to DXR was primary and secondary hyperparathyroidism. Most of the women with these conditions were previously undiagnosed, indicating that further follow-up of patients with low age-adjusted DXR BMD is justified.

Effect of Surgery Versus Observation: Skeletal 5-Year Outcomes in a Randomized Trial of Patients With Primary HPT (the SIPH Study).

Mild primary hyperparathyroidism (PHPT) is known to affect the skeleton, even though patients usually are asymptomatic. Treatment strategies have been widely discussed. However, long-term randomized studies comparing parathyroidectomy to observation are lacking. The objective was to study the effect of parathyroidectomy (PTX) compared with observation (OBS) on bone mineral density (BMD) in g/cm2 and T-scores and on biochemical markers of bone turnover (P1NP and CTX-1) in a prospective randomized controlled study of patients with mild PHPT after 5 years of follow-up. Of 191 patients with mild PHPT randomized to either PTX or OBS, 145 patients remained for analysis after 5 years (110 with validated DXA scans). A significant decrease in P1NP (p < 0.001) and CTX-1 (p < 0.001) was found in the PTX group only. A significant positive treatment effect of surgery compared with observation on BMD (g/cm2 ) was found for the lumbar spine (LS) (p = 0.011), the femoral neck (FN) (p < 0.001), the ultradistal radius (UDR) (p = 0.042), and for the total body (TB) (p < 0.001) but not for the radius 33% (Rad33), where BMD decreased significantly also in the PTX group (p = 0.012). However, compared with baseline values, there was no significant BMD increase in the PTX group, except for the lumbar spine. In the OBS group, there was a significant decrease in BMD (g/cm2 ) for all compartments (FN, p < 0.001; Rad33, p = 0.001; UDR, p = 0.006; TB, p < 0.001) with the exception of the LS, where BMD was stable. In conclusion, parathyroidectomy improves BMD and observation leads to a small but statistically significant decrease in BMD after 5 years. Thus, bone health appears to be a clinical concern with long-term observation in patients with mild PHPT. © 2017 American Society for Bone and Mineral Research.

FGF23, metabolic risk factors, and blood pressure in patients with primary hyperparathyroidism undergoing parathyroid adenomectomy.

BACKGROUND: Fibroblast growth factor-23 (FGF23), a regulator of secretion of parathyroid hormone (PTH), is implicated in the development of cardiovascular disease. The role of FGF23 in primary hyperparathyroidism (pHPT) is unclear. METHODS: A total of 150 consecutive patients with pHPT were examined with ambulatory blood pressure monitoring ((24h)ABP) before parathyroid adenomectomy (PTX). Blood samples were collected 6 ± 2 weeks before and 6 ± 2 weeks after PTX. RESULTS: Plasma FGF23 levels decreased after PTX from a median of 45.2 pg/mL (interquartile range 37.6-54.8) to 36.8 pg/mL (26.7-48.7); P < .001. This postoperative decrease correlated with the decrease in ionized calcium (r = 0.24; P < .01). Greater FGF23 concentrations at baseline were associated with a greater weight of the adenoma and PTH levels, as well as with body mass index, triglycerides, and insulin levels and greater postoperative decreases in FGF23, ionized calcium, insulin growth-like factor 1, and insulin. FGF23 and PTH both correlated with greater blood pressures on (24h)ABP, especially at nighttime (r = 0.31 and r = 0.28; P ≤ .01), whereas after multivariate adjustment, only PTH remained independently associated with (24)ABP. CONCLUSION: Circulating FGF23 is increased in pHPT and is associated independently with the metabolic risk profile. The long-term benefit of decreasing FGF23 in pHPT after PTX remains to be established.

Tumour nuclear oestrogen receptor beta 1 correlates inversely with parathyroid tumour weight.

Primary hyperparathyroidism (PHPT) is a common endocrinopathy, frequently caused by a parathyroid adenoma, rarely by a parathyroid carcinoma that lacks effective oncological treatment. As the majority of cases are present in postmenopausal women, oestrogen signalling has been implicated in the tumourigenesis. Oestrogen receptor beta 1 (ERB1) and ERB2 have been recently identified in parathyroid adenomas, the former inducing genes coupled to tumour apoptosis. We applied immunohistochemistry and slide digitalisation to quantify nuclear ERB1 and ERB2 in 172 parathyroid adenomas, atypical adenomas and carcinomas, and ten normal parathyroid glands. All the normal parathyroid glands expressed ERB1 and ERB2. The majority of tumours expressed ERB1 (70.6%) at varying intensities, and ERB2 (96.5%) at strong intensities. Parathyroid carcinomas expressed ERB1 in three out of six cases and ERB2 in five out of six cases. The intensity of tumour nuclear ERB1 staining significantly correlated inversely with tumour weight (P=0.011), and patients whose tumours were classified as ERB1-negative had significantly greater tumour weight as well as higher serum calcium (P=0.002) and parathyroid hormone levels (P=0.003). Additionally, tumour nuclear ERB1 was not expressed differentially with respect to sex or age of the patient. Levels of tumour nuclear ERB2 did not correlate with clinical characteristics. In conclusion, decreased ERB1 immunoreactivity is associated with increased tumour weight in parathyroid adenomas. Given the previously reported correlation with tumour-suppressive signalling, selective oestrogen receptor modulation (SERMs) may play a role in the treatment of parathyroid carcinomas. Future studies of SERMs and oestrogen treatment in PHPT should consider tumour weight as a potential factor in pharmacological responsiveness.

Effects of parathyroidectomy versus observation on the development of vertebral fractures in mild primary hyperparathyroidism.

CONTEXT: Mild primary hyperparathyroidism (PHPT) is a common disease especially in middle-aged and elderly women. The diagnosis is frequently made incidentally and treatment strategies are widely discussed. OBJECTIVE: To study the effect of parathyroidectomy (PTX) compared with observation (OBS) on biochemistry, safety, bone mineral density (BMD), and new fractures. DESIGN: Prospective, randomized controlled study (SIPH study), with a 5-year follow-up. SETTING: The study was conducted at multicenter, tertiary referral centers. PATIENTS: Of 191 randomized patients with mild PHPT, biochemical data were available for 145 patients after 5 years, with a mean age at inclusion of 62.8 years (OBS group, 9 males) and 62.1 years (PTX group, 10 males). INTERVENTION: Parathyroidectomy vs observation. MAIN OUTCOME MEASURES: Biochemistry, BMD, and new radiographic vertebral fractures. RESULTS: Serum-calcium and PTH-levels normalized after surgery and did not deteriorate by observation. BMD Z-scores were normal at inclusion in the lumbar spine (LS) and femoral neck (FN). For LS, BMD Z-scores were stable for 5 years with observation, but decreased in FN (P < .02). After surgery, BMD Z-scores increased significantly in both compartments (P < .02 for both), with a highly significant treatment effect of surgery compared to observation (P < .001). During follow-up, five new clinically unrecognized vertebral fractures were found in 5 females, all in the OBS group (P = .058). CONCLUSION: Even though new vertebral fractures occurred only in the observation group, the frequency was not significantly different from the surgery group. Longer follow-up is needed before firm conclusions can be drawn about the long-term safety of observation, as opposed to surgery.

Health-related quality of life after successful surgery for primary hyperparathyroidism: no additive effect from vitamin D supplementation: results of a double-blind randomized study.

OBJECTIVE: Vitamin D insufficiency is common in primary hyperparathyroidism (pHPT). Patients with pHPT frequently have a reduced health-related quality of life (HRQoL). Our objectives were to evaluate whether HRQoL in pHPT is associated with vitamin D insufficiency and whether vitamin D supplementation after parathyroidectomy (PTX) could improve HRQoL. DESIGN: A randomized, double-blind study (ClinicalTrials.gov identifier: NCT00982722). METHODS: The study included 150 pHPT patients randomized, 6 weeks after PTX, to daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg (D+) or calcium carbonate alone (D-). HRQoL was estimated with SF-36 before and after PTX and after 12 months of study medication. RESULTS: Three-quarters (77%) of the pHPT patients had vitamin D insufficiency, defined as 25OHD <50 nmol/l. The pHPT patients scored lower than a reference population in all domains of SF-36. A total of 135 patients completed the entire study period. Improvements in nearly all domains were registered at the follow-up 6 weeks after PTX. At the end of the study medication period, the D+ group had a significantly higher median serum (s-) 25OHD concentration (76 (65; 93) (lower; upper interquartile ranges) vs 48 (40; 62) nmol/l, P<0.001) and a lower plasma (p-) parathyroid hormone concentration (40 (34; 52) vs 49 (38; 66) ng/l, P=0.01) than the D- group. The improvements in HRQoL remained unchanged at the follow-up 1 year after PTX. Postoperative vitamin D supplementation had no obvious effect on HRQoL. CONCLUSION: PTX resulted in significant improvements in HRQoL. Despite a high prevalence of vitamin D insufficiency, 1 year of postoperative vitamin D supplementation had no obvious beneficial effect on HRQoL.

Vitamin D supplementation after parathyroidectomy: effect on bone mineral density-a randomized double-blind study.

Patients with primary hyperparathyroidism (PHPT) have higher bone turnover, lower bone mineral density (BMD), and an increased risk of fractures. They also have a high incidence of low vitamin D levels (25-OH-vitamin D <50 nmol/L) that could worsen the negative effect on the bone. In this double-blinded clinical trial, 150 patients with PHPT were randomized, after successful parathyroidectomy (PTX), to 1-year daily treatment with either cholecalciferol 1600 IU and calcium carbonate 1000 mg (D+) or calcium carbonate alone (D-). BMD was measured in the lumbar spine, femoral neck, total hip, distal and 33% radius using dual-energy X-ray absorptiometry (DXA) before surgery and after 1 year of study medication. Median age was 60 (range 30-80) years and there were 119 (79%) women and 31 (21%) men; 76% had 25-OH-D <50 nmol/L before PTX and 50% had persistent elevated parathyroid hormone (PTH) 6 weeks after PTX. A similar increase in BMD in the lumbar spine, femoral neck, and total hip was observed in both groups (D+ : 3.6%, 3.2%, and 2.7%, p<0.001, respectively; and D-: 3.0%, 2.3%, and 2.1%, respectively, p<0.001). Patients with vitamin D supplementation also increased their BMD in distal radius (median 2.0%; interquartile range, -1.7% to 5.4%; p=0.013). The changes in BMD, especially in the hips, were correlated to the baseline concentrations of PTH, ionized calcium, and bone markers (p<0.001). A benefit from vitamin D substitution was observed among patients with a persistent postoperative PTH elevation, who also improved their BMD at 33% radius and radius ultradistal (p<0.05). In conclusion, except for a minor improvement of radius BMD, our data show no beneficial effect on BMD or bone turnover markers of vitamin D supplementation after PTX. Preoperative PTH seems to have the strongest association with improvement in BMD.

Primary hyperparathyroidism and metabolic risk factors, impact of parathyroidectomy and vitamin D supplementation, and results of a randomized double-blind study.

BACKGROUND: Vitamin D insufficiency may increase the risk for cardio metabolic disturbances in patients with primary hyperparathyroidism (PHPT). OBJECTIVE: To analyze the vitamin D status and indices of the metabolic syndrome in PHPT patients and the effect of vitamin D supplementation after parathyroid adenomectomy (PTX). DESIGN AND METHODS: Double-blinded, randomized clinical trial (ClinicalTrials.gov identifier: NCT00982722) performed at Karolinska University Hospital, Sweden, April 2008 to November 2011. One hundred and fifty consecutive patients with PHPT (119 women) were randomized after PTX, 75 to oral treatment with calcium carbonate 1000 mg daily and 75 to calcium carbonate 1000 mg and cholecalciferol 1600 IU daily over 12 months. Changes in metabolic profile and ambulatory blood pressure (BP) were analyzed. Main outcome measures were changes in metabolic factors, BP, and body composition. RESULTS: The 25-hydroxyvitamin D (25-OH-D)-level was <50 nmol/l in 76% of the patients before PTX. After PTX, glucose, insulin, and IGF1 decreased, while the 25-OH-D and the IGF-binding protein 1 increased and remained unchanged at follow-up after study medication. One year of vitamin D supplementation resulted in lower parathyroid hormone (PTH) (40 (34-52) vs 49 (38-66) ng/l) and higher 25-OH-D (76 (65-93) vs 49 (40-62) nmol/l; P<0.05). Other laboratory parameters were stable compared with after PTX. Systolic BP decreased and total bone mineral content increased in both groups. CONCLUSION: Except for the lowering of the PTH level, no additive effect of vitamin D supplementation was seen. However, PTX proved effective in reducing insulin resistance.

Functioning and quality of life in adults with mild-to-moderate osteogenesis imperfecta.

PURPOSE: The aim of this study was to describe physical activity, quality of and satisfaction with life, pain, joint mobility and muscle function in adults with mild-to-moderate osteogenesis imperfecta (OI) to form the basis of improved clinical care and physical therapy treatment. METHOD: A total of 40 men and women aged between 21 and 71 years were identified and a prospective, cross-sectional study was performed on 29 (18 women) included participants. The participants had to be able to walk and to have a diagnosis of mild-to-moderate OI. Self-administered questionnaires and clinical examinations were used. RESULTS: Difficulties were found in all domains of the International Classification of Functioning, Activity and Health. Pain was reported in 25 of 29 participants and scoliosis was found in 23 participants. Difficulty to run was estimated in 18 participants. A total of 19 of 27 participants reported reaching the recommendations of 30 min of moderate-intensity activity preferably every day. Life satisfaction was high even though health-related quality of life, assessed with the Short Form 36, was significantly lower than the Swedish norm. CONCLUSION: Impairments and activity limitations involved pain, scoliosis, contractures as well as trouble with running, heavy lifting, heavy work and sports. This study show that individuals with mild-to-moderate OI perceive themselves as having decreased health-related quality of life and this seems to depend on decreased physical functioning. Despite that, as a group, they estimated high life satisfaction and 19 participants reported adhering to the general recommendation of 30 min of moderate-intensity activity preferably every day.

Associations between amino acids and bone mineral density in men with idiopathic osteoporosis.

Idiopathic osteoporosis in middle-aged men is characterized by low-level bone formation. Inhibited anabolism may be involved in the pathogenesis of the disease and amino acids may be of importance. In the present study fasting amino acid profiles in plasma and erythrocytes were determined in 22 male idiopathic osteoporosis (MIO) patients and in 20 age-matched healthy men and associated with bone mineral density, bone histomorphometry and hormones. The osteoporotic patients had normal plasma essential amino acids but increased non-essential amino acids (p=0.001), particularly glutamine and glycine. The ratio essential/non-essential amino acids, an index of protein nutritional status, was decreased in the MIO patients (0.59 (0.04) µmol/l, mean (SD)), compared to controls (0.66 (0.05), p=0.001). In the MIO patients, the ratio essential/non-essential plasma amino acids (r=0.60, p=0.003) was positively correlated with lumbar spine bone mineral density. The erythrocyte amino acids represent a large proportion of the free amino acids in blood. A novel finding was the lower levels of erythrocyte tryptophan in MIO (12 (2) µmol/l) compared to controls (16 (3), p=0.001) and decreased erythrocyte/plasma ratio (0.28 (0.07) vs. 0.33, (0.06), p<0.01), suggesting an altered amino acid transport of tryptophan between plasma and erythrocytes. In the combined group of MIO and control men (n=42), bone mineral density was positively correlated with erythrocyte tryptophan in both the lumbar spine (r=0.45, p=0.003) and femoral neck (r=0.56, p<0.001). The bone histomorphometric variables wall thickness, trabecular thickness and mineral apposition rate were all positively associated with erythrocyte tryptophan levels in the MIO patients. In the combined group of MIO and controls, a multiple regression analysis showed that erythrocyte tryptophan could explain 22% of the variation of lumbar spine and 30% of the variation in femoral neck bone mineral density. We conclude that men with idiopathic osteoporosis have changes in free amino acid profiles which indicate their altered utilization. The correlations between tryptophan and bone mineral density and bone histomorphometry suggest a link between tryptophan and osteoblast function which may be important for bone health.

Effect of surgery on cardiovascular risk factors in mild primary hyperparathyroidism.

CONTEXT: Mild primary hyperparathyroidism (pHPT) seems to have a good prognosis, and indications for active treatment (surgery) are widely discussed. The extraskeletal effects of PTH, such as insulin resistance, arterial hypertension, and cardiovascular (CV) risk, may however be reversible by operation. OBJECTIVE: Our aim was to study biochemical markers of bone turnover, indices of the metabolic syndrome, and various risk markers for CV disease in patients with mild pHPT randomized to observation without surgery or operative treatment and followed for 2 yr. DESIGN/SETTING/PATIENTS: A total of 116 patients (mean age, 63 +/- 8 yr; 19 men and 97 women) who on May 1, 2008, had performed the 2-yr visit in a randomized study on mild pHPT (serum calcium at baseline, 2.69 +/- 0.11 mmol/liter) and where frozen samples were available from baseline and follow-up participated in the study. RESULTS: Calcium and PTH levels were normalized after surgery, and biochemical markers of bone turnover decreased by 35%, followed by a significant increase in BMD in the spine (2.7%; P < 0.01) and femoral neck (1.1%; P < 0.02) compared with the observation group. No significant differences were observed between the groups for blood pressure, markers of insulin resistance, detailed cholesterol metabolism, adipokines, or parameters of inflammation and CV surrogate markers. CONCLUSIONS: We observed expected effects on biochemical markers of bone turnover and bone mass after surgical treatment of mild pHPT, with stable values in the group randomized to observation. For a variety of measures of the metabolic syndrome, adipokines, and CV risk factors, no benefit of operative treatment could be demonstrated. Neither did we observe any deleterious effects of conservative management in the 2-yr perspective.

Bone histomorphometry in male idiopathic osteoporosis.

The pathogenesis of male osteoporosis at the cellular level is still elusive. We performed histomorphometric analysis of bone biopsy samples from 51 eugonadal men with idiopathic osteoporosis. Their median age was 54 (range 29-73) years. Eighty-two percent of the patients had a fracture history, and 57% had vertebral fractures. Bone volume, trabecular thickness, wall thickness, and osteoid thickness were significantly reduced in osteoporotic men compared with healthy men. Erosion depth was similar, as were the bone remodeling parameters such as bone formation rate, mineral apposition rate, and activation frequency. In the osteoporotic men, osteoid thickness was correlated to bone mineral density at the lumbar spine (R(2) = 0.19, P < 0.01); together with wall thickness, the two parameters could explain 27% of the variation in lumbar spine bone mineral density. The osteoid thickness was correlated to anthropometric variables such as body weight (R(2) = 0.24, P < 0.001) and body mass index (R(2) = 0.14, P < 0.01), as well as to serum estradiol levels (R(2) = 0.14, P < 0.01) and to the ratio insulin-like growth factor-1 (IGF-1) to IGF-binding protein-1 (IGFBP-1) (R(2) = 0.12, P < 0.01). Regression analysis showed that 36% of the variation in osteoid thickness could be predicted by body weight and estradiol levels. In conclusion, bone histomorphometry in male idiopathic osteoporosis was characterized by thin bone structural units, which might suggest osteoblast dysfunction. Bone histomorphometry parameters were associated with low body weight, low estradiol levels, and increased levels of IGFBP-1, supporting the notion that estrogens and IGFs play regulatory roles in male bone turnover.