Real-World Effectiveness of Anti-Resorptive Treatment in Patients With Incident Fragility Fractures-The STORM Cohort-A Swedish Retrospective Observational Study.

Results from real-world evidence (RWE) from the largest healthcare region in Sweden show low uptake of antiresorptive (AR) treatment, but beneficial effect in those receiving treatment, especially for the composite outcome of hip fracture or death. For RWE studies, Sweden is unique, with virtually complete coverage of electronic medical records (EMRs) and both regional and national registries, in a universal publicly funded healthcare system. To our knowledge, there is no previous RWE study evaluating the efficacy of AR treatment compared to no AR treatment after fragility fracture, including data on parenteral treatments administered in hospital settings. The Stockholm Real World Management (STORM) study cohort was established in the healthcare region of Stockholm to retrospectively assess the effectiveness of AR treatment after first fragility fracture using the regional EMR system for both hospital and primary care. Between 2012 and 2018, we identified 69,577 fragility fracture episodes among 59,078 patients, men and women, 50 years and older. Of those, 21,141 patients met inclusion and exclusion criteria (eligible cohort). From these, the final matched study cohort comprised 9840 fragility fractures (cases receiving AR treatment [n = 1640] and controls not receiving AR treatment [n = 8200]). Propensity scores were estimated using logistic regression models with AR treatment as outcome and confounders as independent variables followed by analysis using Cox proportional hazard models. Real world evidence from Sweden's largest healthcare region, comprising a quarter of the Swedish population, show that only 10% of patients receive AR treatment within 1 year after a fragility fracture. Factors associated with not receiving treatment include having a diagnosis of cardiovascular disease. In those treated, AR have positive effects particularly on the composite of fracture and death (any fracture/death and hip fracture/death) in individuals matched for all major confounders. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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.

GRADE guidelines 6. Rating the quality of evidence--imprecision.

GRADE suggests that examination of 95% confidence intervals (CIs) provides the optimal primary approach to decisions regarding imprecision. For practice guidelines, rating down the quality of evidence (i.e., confidence in estimates of effect) is required if clinical action would differ if the upper versus the lower boundary of the CI represented the truth. An exception to this rule occurs when an effect is large, and consideration of CIs alone suggests a robust effect, but the total sample size is not large and the number of events is small. Under these circumstances, one should consider rating down for imprecision. To inform this decision, one can calculate the number of patients required for an adequately powered individual trial (termed the "optimal information size" [OIS]). For continuous variables, we suggest a similar process, initially considering the upper and lower limits of the CI, and subsequently calculating an OIS. Systematic reviews require a somewhat different approach. If the 95% CI excludes a relative risk (RR) of 1.0, and the total number of events or patients exceeds the OIS criterion, precision is adequate. If the 95% CI includes appreciable benefit or harm (we suggest an RR of under 0.75 or over 1.25 as a rough guide) rating down for imprecision may be appropriate even if OIS criteria are met.

Testing the HTA core model: experiences from two pilot projects.

OBJECTIVES: The aim of this study was to analyze and describe process and outcomes of two pilot assessments based on the HTA Core Model, discuss the applicability of the model, and explore areas of development. METHODS: Data were gathered from HTA Core Model and pilot Core HTA documents, their validation feedback, questionnaires to investigators, meeting minutes, emails, and discussions in the coordinating team meetings in the Finnish Office for Health Technology Assessment (FINOHTA). RESULTS: The elementary structure of the HTA Core Model proved useful in preparing HTAs. Clear scoping and good coordination in timing and distribution of work would probably help improve applicability and avoid duplication of work. CONCLUSIONS: The HTA Core Model can be developed into a platform that enables and encourages true HTA collaboration in terms of distribution of work and maximum utilization of a common pool of structured HTA information for national HTA reports.

Medical observation, compared with parathyroidectomy, for asymptomatic primary hyperparathyroidism: a prospective, randomized trial.

CONTEXT: The clinical presentation of primary hyperparathyroidism (pHPT) has changed during the last half century, and the diagnosis is now more often made by chance in patients with no specific symptoms. OBJECTIVE: The present study is a randomized, controlled trial that investigates the effects of parathyroidectomy or medical observation in mild asymptomatic pHPT on morbidity and quality of life (QoL). DESIGN/SETTING/PATIENTS: A total of 191 patients (26 men) with asymptomatic pHPT [mean age 64.2 +/- 7.4 (sd) yr] were recruited in the study and randomized to medical observation (serum calcium level 2.69 +/- 0.08 mmol/liter) or surgery (2.70 +/- 0.08 mmol/liter). We here report baseline and 1 (n = 119) and 2 yr data (n = 99) on those who had completed the follow-up visits by the end of the inclusion period. RESULTS: At baseline, the patients had significantly lower QoL (SF-36) and more psychological symptoms, compared with age- and sex-matched healthy subjects. The two groups were similar at baseline, and no clinically significant changes in these parameters were seen during the observation time. Calcium and PTH normalized after surgery. The areal bone mineral density increased in the group randomized to operation, whereas the bone mineral density remained stable in the medical observation group. No change in kidney function (creatinine) or blood pressure was observed longitudinally or between the groups. CONCLUSIONS: Asymptomatic patients with mild pHPT have decreased QoL and more psychological symptoms than normal controls. No benefit of operative treatment, compared with medical observation, was found on these measures so far.

Primary hyperparathyroidism is common in postmenopausal women with forearm fracture and low bone mineral density.

OBJECTIVE: The most common etiologies of osteoporosis in women are estrogen deficiency and, later on in life, the functional changes caused by aging. There are, however, numerous causes of secondary bone loss. Little is known about the prevalence of concomitant disease in women with distal forearm fracture, which is the most common of the classical osteoporotic fractures. METHOD: Postmenopausal healthy women between 45 and 65 years of age with a forearm fracture were invited to join a prospective randomized study evaluating the effect of physical training on bone mineral density. The main inclusion criteria were previous forearm fracture and BMD T-score in the interval -1 to -3.0. Of the 167 postmenopausal women with a forearm fracture, 23% had a normal BMD, 59% had osteopenia, and 18% had osteoporosis. RESULTS: Of the 119 patients meeting the BMD criteria for inclusion, one patient was found to have sprue, two were diagnosed with thyreotoxicos, and eight had primary hyperparathyroidism. The prevalence of primary hyperparathyroidism in this population was 6.7%, and thus three times higher than that previously observed in healthy Swedish postmenopausal women. CONCLUSION: The data suggest an increased prevalence of primary hyperparathyroidism in women with forearm fracture and low bone mass, and imply the importance of basic laboratory screening in this population.

Bioelectrical impedance underestimates total and truncal fatness in abdominally obese women.

OBJECTIVE: To compare estimates of total and truncal fatness from eight-electrode bioelectrical impedance analysis equipment (BIA(8)) with those from DXA in centrally obese women. The secondary aim was to examine BMI and waist circumference (WC) as proxy measures for percentage total body fat (%TBF) and truncal body fat percentage (tr%BF). RESEARCH METHODS AND PROCEDURES: This was a cross-sectional study of 136 women (age, 48.1 +/- 7.7 years; BMI, 30.4 +/- 2.9 kg/m(2); %TBF(DXA), 46.0 +/- 3.7%; WC, 104 +/- 8 cm). Fatness was measured by DXA and Tanita BC-418 equipment (Tanita Corp., Tokyo, Japan). Agreement among methods was assessed by Bland-Altman plots, and regression analysis was used to evaluate anthropometric measures as proxies for total and abdominal fatness. RESULTS: The percentage of overweight subjects was 41.9%, whereas 55.9% of the subjects were obese, as defined by BMI, and all subjects had a WC exceeding the World Health Organization cut-off point for abdominal obesity. Compared with DXA, the BIA(8) equipment significantly underestimated total %BF (-5.0; -3.6 to -8.5 [mean; 95% confidence interval]), fat mass (-3.6; -3.9 to -3.2), and tr%BF (-8.5; -9.1 to -7.9). The discrepancies between the methods increased with increasing adiposity for both %TBF and tr%BF (both p < 0.001). Variation in BMI explained 28% of the variation in %TBF(DXA) and 51% of %TBF(BIA8). Using WC as a proxy for truncal adiposity, it explained only 18% of tr%BF(DXA) variance and 27% of tr%BF(BIA8) variance. The corresponding figures for truncal fat mass were 49% and 35%, respectively. No significant age effects were observed in any of the regressions. DISCUSSION: BIA(8) underestimated both total and truncal fatness, compared with DXA, with higher dispersion for tr%BF than %TBF. The discrepancies increased with degree of adiposity, suggesting that the accuracy of BIA is negatively affected by obesity.

The effect of physical training on bone mineral density in women with endometriosis treated with GnRH analogs: a pilot study.

BACKGROUND: The effect of physical training on bone mineral density (BMD) in women with endometriosis treated with gonadotropin-releasing hormone (GnRH) analogs was studied. METHODS: Nineteen Caucasian premenopausal women aged 23-38 years were included in the study. The subjects were all treated with 21.6 mg goserelin during 6 months. The patients were randomized to physical training n=8 or to a control group n=11. The total period of training was 12 months, whereas GnRH treatment was terminated after 6 months. BMD was measured in the femoral neck area and the lumbar spine using dual X-ray absorptiometry (DEXA). This was performed just before treatment, after 6 months and after 12 months. Six women fulfilled the training during 12 months of observation. In the control group 10 women were followed up for 12 months. RESULTS: After 6 months the women in the physical training group were 2.1% below baseline. Six months later these women had gained BMD in the femoral neck and were 0.6% below baseline. Those in the control group lost 2.8% after 6 months and were 3.6% below baseline after 12 months. The difference in loss of BMD after 12 months between the groups was significant 0.029. In the spine there was no significant difference between the two groups. CONCLUSIONS: Physical training in women with endometriosis was found to rebuild bone after treatment with GnRH analogs when compared to a control group. This effect could be demonstrated 6 months after cessation of GnRH treatment.

Physical training and hormone replacement therapy reduce the decrease in bone mineral density in perimenopausal women: a pilot study.

The effects of physical training and hormone replacement therapy (HRT) on bone mineral density in perimenopausal women were studied. Sixty perimenopausal women were randomized to either physical training (n = 20), HRT (n = 20), or control group (n = 20). The study period was 18 months. Bone mineral density (BMD) in the femoral neck and lumbar spine was measured using dual-energy X-ray absorptiometry (DXA). DXA was performed before treatment and after 6 and 18 months. Blood samples for analysis of the bone markers U-deoxypyridinoline and osteocalcin were collected at the same time points. After 18 months, BMD in the spine had not decreased in either the training group or in the HRT group. In the control group, spine BMD had significantly decreased (p = 0.0014). U-Deoxypyridinoline and osteocalcin were increased significantly in the control group (p = 0.0198, p = 0.0295, respectively). No significant changes in bone marker levels were found in the training group or the HRT group. We found that both HRT and physical training can prevent loss of spine BMD in perimenopausal women over a period of 18 months. HRT remains a cornerstone in the treatment of vasomotor symptoms and preservation of BMD. However, HRT can only be used for limited periods of time due to the potential serious adverse effects. This study indicates a beneficial effect of physical activity on spine BMD in the perimenopausal period, and highlights its potential as an alternative to HRT during this period.

Effects of estradiol and estradiol sulfamate on the liver of ovariectomized or ovariectomized and hypophysectomized rats.

This study was performed to evaluate and compare the effects of estradiol sulfamate (J995) and estradiol (E2) on the hepatic levels of the estrogen receptor (ER) and its mRNA, in ovariectomized (OVX) and OVX+hypophysectomized (OVXHX) female rats and to study the effects on the liver-derived serum compounds angiotensin I, triglycerides, high-density lipoprotein (HDL) and cholesterol. ER concentrations were determined using ligand-binding assay (LBA) and enzyme immuno assay (EIA), and the mRNA levels using solution hybridization. The rats were treated orally (p.o.) or subcutaneously (s.c.) for 7 days, with treatments initiated 14 days after surgery. No differences were found in ER mRNA levels between J995 and E2 treated rats. The s.c. administered estrogens increased ER levels in OVX rats. Addition of GH+DEX to OVXHX rats restored the ER to levels above those seen in intact rats, whereas simultaneous oral treatment with E2 significantly decreased ER levels again. The s.c. treatment with either J995 or E2 limited the increase caused by addition of GH+DEX. After oral treatment angiotensin I levels were increased by E2, but not by J995, while triglycerides, HDL and cholesterol levels were decreased by oral E2, J995 showing a similar pattern but was less effective. In summary, these results on hepatic ER levels and estrogen dependent compounds produced by the liver showed that J995 has a lower impact on the normal liver functions after oral treatment than E2. Thus, J995 is a very promising substance for development of oral estrogen treatment with reduced hepatic side effects.