Impact of 3-Monthly Vitamin D Supplementation Plus Exercise on Survival after Surgery for Osteoporotic Hip Fracture in Adult Patients over 50 Years: A Pragmatic Randomized, Partially Blinded, Controlled Trial.

OBJECTIVE: To determine whether 3-monthly supplementation of an oral vitamin D widely used in Spain (calcifediol) plus daily exercise could influence survival at one and four years after surgery for osteoporotic hip fracture. DESIGN: A pragmatic, randomized, partially single-blind placebo-controlled study. SETTING: Patients admitted to a tertiary university hospital for acute hip fracture. PARTICIPANTS: 675 healthy adult patients undergoing surgery for osteoporotic hip fracture were recruited from January 2004 to December 2007. INTERVENTION: Patients were randomized to receive either 3-monthly oral doses of 3 mg calcifediol (Hidroferol Choque®) or placebo in the 12 months postsurgery. Patients who received calcifediol were also given an exercise programme. The placebo group received standard health recommendations only. MEASUREMENTS: The primary endpoint was survival at 1 year and at 4 year follow-up. We also recorded new fractures, medical complications and anti-osteoporotic treatment compliance. RESULTS: We included a total of 88 patients, aged 62 to 99 years. Mean age was 82 years and 88.6% were women. At 12 months, 10 (11.3%) patients had died, 9 of them, from the non-intervention group. At 4 years after surgery, 20 (22.7%) had died, 3 (3.4%) from the intervention group and 17 (19.3%) from the non-intervention group. At this time, survival curve analysis showed 93% survival in the intervention group and 62% in the non-intervention group (p=0.001). At 12-month follow up, there were 18 new fractures, 9 in each group. The non-intervention group had more medical complications, with significant differences at visit 2 (p = 0.04) and 3 (p = 0.02) but not at visit 4 (p = 0.18). No significant differences between groups were found regarding treatment compliance. CONCLUSION: 3-monthly, oral supplements of 3 mg calcifediol plus daily exercise improved survival at one-year and four-year follow up after surgery for an osteoporotic hip fracture.

Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk.

CONTEXT: The FREEDOM (Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months) trial showed denosumab significantly reduced the risk of fractures in postmenopausal women with osteoporosis. OBJECTIVE: We evaluated the effect of denosumab on the incidence of new vertebral and hip fractures in subgroups of women at higher risk for these fractures. DESIGN: FREEDOM was a 3-yr, randomized, double-blind, placebo-controlled, phase 3 trial. PARTICIPANTS AND SETTING: Postmenopausal women (N = 7808) with osteoporosis were enrolled at 213 study sites worldwide. INTERVENTIONS: Subjects received s.c. denosumab (60 mg) or placebo every 6 months and daily supplements of calcium (≥1000 mg) and vitamin D (≥400 IU). MAIN OUTCOME MEASURES: This post hoc analysis evaluated fracture incidence in women with known risk factors for fractures including multiple and/or moderate or severe prevalent vertebral fractures, aged 75 yr or older, and/or femoral neck bone mineral density T-score of -2.5 or less. RESULTS: Compared with placebo, denosumab significantly reduced the risk of new vertebral fractures in women with multiple and/or severe prevalent vertebral fractures (16.6% placebo vs. 7.5% denosumab; P < 0.001). Similarly, denosumab significantly reduced the risk of hip fractures in subjects aged 75 yr or older (2.3% placebo vs. 0.9% denosumab; P < 0.01) or with a baseline femoral neck bone mineral density T-score of -2.5 or less (2.8% placebo vs. 1.4% denosumab; P = 0.02). These risk reductions in higher-risk individuals were consistent with those seen in patients at lower risk of fracture. CONCLUSIONS: Denosumab reduced the incidence of new vertebral and hip fractures in postmenopausal women with osteoporosis at higher risk for fracture. These results highlight the consistent antifracture efficacy of denosumab in patients with varying degrees of fracture risk.

Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation.

Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60 mg/day, and 2,572 raloxifene 120 mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer.

Sunscreen and risk of osteoporosis in the elderly: a two-year follow-up.

BACKGROUND: It has been suggested that the use of sunscreens to prevent skin cancer may put the population at risk of vitamin D deficiency, which in turn may lead to secondary hyperparathyroidism, loss of cortical bone and, ultimately, osteoporotic fractures. OBJECTIVE: To investigate whether sunscreen SPF15 may lead to loss of bone mass. METHODS: We followed 10 sunscreen users and 18 controls over 2 years, including two summers, two winters and a basal period (winter). Bone mass was evaluated each season with dual x-ray absorptiometry. RESULTS: During follow-up, mild fluctuations in bone mass could be seen at Ward's site in both groups, without a definitive pattern. At the final visit, no significant loss of bone mass was observed in sunscreen users or in the control group. We did not observe any significant differences between groups throughout the study. CONCLUSION: Although the study samples in this work are small, and a slight variation in bone mass may not be detected, in a clinical setting, sunscreen SPF15 protection does not seem to increase the risk of osteoporosis.

Thymic carcinoid and parathyroid hyperplasia detection with 99mTc-MIBI men type 1.

We report a case of a 35-year-old male, with a history of diarrhea, renal lithiasis with frequent expulsions of calculus and hypercalcemia during the last 2 years. The patient was studied and diagnosed with a multiple endocrine neoplasia type I (MEN I), familiar (mother with MEN I). A scintigraphic study with 99mTc-MIBI was performed in order to localize hyperfunctioning parathyroid glands because of biochemical diagnosis of primary hyperparathyroidism. Double phase 99mTc-MIBI scan detected one hyperfunctioning parathyroid gland and a large anterior mediastinal mass. Subsequent, plain radiograph and CT of the chest showed a soft-tissue mass in that localization. Punch biopsy of the lesion guided by CT revealed malignant cells of neuroendocrine tumor. The tumor was removed and histologically confirmed as a carcinoid within a thymus in a MEN type I syndrome. MEN I patients can benefit from the examination with this agent which can potentially localize not only parathyroid endocrine pathology but also unknown associated tumors.

[Isotopic study with double phase 99mTc-sestamibi in the localization of parathyroid gland lesions]. / Exploración isotópica con 99mTc-sestamibi en doble fase en la localización de lesiones de las glándulas paratiroides.

BACKGROUND: The use of preoperative imaging in patients with hyperparathyroidism remains controversial. The aim of this study is to assess the usefulness of the double-phase 99mTc-sestamibi scintigraphy in the diagnosis of abnormal parathyroid glands in patients with primary hyperparathyroidism. PATIENTS AND METHODS: We studied 60 patients presenting with primary hyperparathyroidism who were referred to surgery; four of them had been unsuccessfully operated. 99mTc-sestamibi scintigraphy were performed in all patients previously to surgery. Scintigraphic technique: planar imaging of the neck and thorax was done in the anterior view at 15 and 150 min postinjection of 740 MBq (20 mCi) of 99mTc-sestamibi. RESULTS: Surgery found 57 adenomas (2.59 [SD, 5.84] g; range 0.160-40), 6 hyperplastic glands (0.34 [SD, 0.26] g) and one carcinoma 8.2 g. The 99mTc-sestamibi was able to localize correctly 60 out of 64 lesions (55/57 adenomas, 4/6 hyperplastic glands and 1/1 carcinoma) (global sensitivity of 94%, adenomas sensitivity of 96%, positive predictive value of 97% and specificity of 98%). Isotopic imaging detected the abnormal tissue in all patients who had undergone unsuccessful previous surgery. PTH (4 [SD, 1.51] pmol/l) and calcium postoperative serum levels (2.13 [SD, 0.22] mmol/l) showed curation of all patients. CONCLUSION: Double phase parathyroid scintigraphy with 99mTc-sestamibi is the method of choice to localize abnormal parathyroid glands.

Clinically prescribed sunscreen (sun protection factor 15) does not decrease serum vitamin D concentration sufficiently either to induce changes in parathyroid function or in metabolic markers.

Some studies have suggested that the use of sunscreens to prevent skin cancer may put the population at risk of vitamin D deficiency. We followed 24 sunscreen users and 19 controls over 2 years, including two summers, two winters and a basal period (winter). Vitamin D, parathormone and bone biological markers were evaluated each season. Mean levels of 25-hydroxyvitamin D rose in summer, with the increments being significantly higher for the second year in the control group. Levels decreased in winter in both groups, and were significantly lower in sunscreen users. We did not observe any significant change in parathormone, tartrate resistant phosphatase, total alkaline phosphatase, osteocalcin, urine hydroxyproline or urine calcium. Clinically prescribed sunscreen creams (sun protection factor 15) caused a minor decrease in 25-hydroxyvitamin D levels, which did not induce secondary hyperparathyroidism or an increment in bone biological markers.

Efficacy of preoperative diagnostic imaging localization of technetium 99m-sestamibi scintigraphy in hyperparathyroidism.

BACKGROUND: Until now, preoperative parathyroid imaging has been considered unnecessary because currently available techniques do not provide any better results than an expert surgeon. We conducted a multicenter prospective study evaluating the capability of technetium 99m sestamibi scintigraphy in the preoperative identification of pathologic glands. METHODS: Ninety-three patients with hyperparathyroidism, seven of them reoperative cases, were studied. In addition, 20 age-matched normocalcemic control subjects were also studied. RESULTS: Surgical confirmation of scintigraphic images was obtained in 91 of 93 cases (sensitivity, 97.8%). In all reoperative cases (n = 7), in all cases of ectopic glands (whether operated or not; n = 6), and in all patients with a single-gland disease (n = 70), topographic identification of the pathologic gland was correct in 100%. In multiple-gland disease (n = 23), involvement of more than one gland was visualized in only 61% of the patients; however, in 91% of patients, at least one gland was localized. Surgical success-defined as postoperative normocalcemia-with this approach was 100%. All scans of normocalcemic control subjects were negative. Of 31 patients in whom a multinodular goiter coexisted, seven presented a significant radionuclide background at 120 minutes' scan. False-positive images were found together with those corresponding to the pathologic glands in only three cases. CONCLUSIONS: 99mTc-sestamibi is a highly reliable, sensitive, and specific technique for imaging of pathologic glands in hyperparathyroidism, especially in single-gland disease. It may be considered as a first line single-procedure when a preoperative topographic diagnosis is required.

Utility of 99mTc-sestamibi scintigraphy as a first-line imaging procedure in the preoperative evaluation of hyperparathyroidism.

OBJECTIVE: The use of preoperative imaging in patients with hyperparathyroidism remains controversial. Many of the available techniques are insufficiently sensitive and specific to justify their routine use. We have evaluated the sensitivity and specificity of 99mTc-sestamibi scintigraphy in the management of patients with different forms of hyperparathyroidism. DESIGN: Preoperative imaging evaluation was carried out by scintigraphic detection of pathological parathyroid glands using 99mTc-sestamibi as a radiotracer; confirmation of scan findings was obtained surgically. PATIENTS: A group of 25 patients with primary (n = 21) or secondary (n = 4) hyperparathyroidism were studied. All were considered for surgical treatment. MEASUREMENTS: In all cases parathyroid imaging was carried out by 99mTc-sestamibi scintigraphy together with at least one other imaging technique which included CT-scan, ultrasonography, MRI or 201TI/99mTc subtraction scintigraphy. Blood tests included measurements of total calcium and PTH. RESULTS: 99mTc-sestamibi scintigraphy correctly localized 20 out of 21 adenomas, giving a sensitivity of 95.2%, markedly higher than that obtained with the other imaging techniques (ultrasonography 75%, 201TI/99mTc subtraction scintigraphy 57.1%, CT-scan 41.7% and MRI 33%). Of a total of 17 glands identified surgically as hyperplastic and confirmed by pathological examination, 99mTc-sestamibi scintigraphy showed a positive image in 10, corresponding always to the larger abnormal glands (sensitivity 58.8%, higher than that observed with the other techniques). No false positive images were obtained with 99mTc-sestamibi. All the ectopic adenomas (n = 3) were identified preoperatively, which contributed significantly to the surgical approach. CONCLUSION: In patients with hyperparathyroidism, 99mTc-sestamibi scintigraphy may be used as the single imaging technique as it shows a very high sensitivity and specificity in the preoperative localization of pathological parathyroid glands; the benefit of localizing parathyroid tissue prior to surgery in cases of ectopic adenomas clearly indicates that when an imaging procedure is required, this technique may be of great help in the management of hyperparathyroidism.

Antigranulocyte bone marrow scans in Paget's disease.

Paget's disease of bone is a disorder of bone remodeling in which excessive production of structurally abnormal bone occurs, with the primary and fundamental abnormality residing in the osteoclast. To evaluate further the jeopardized bone marrow in Paget's disease, the authors studied 29 skeletal lesions by means of conventional bone imaging and antigranulocyte antibody bone marrow imaging in eight consecutive patients affected by Paget's disease. Bone scans showed abnormal tracer uptake in the 29 skeletal sites (11 pelves, 10 vertebrae, 5 extremities, 2 skulls, and 1 rib). Antigranulocyte antibody bone marrow scans showed decreased uptake of radiopharmaceutical in 16 (55%) of those 29 areas (8 pelves, 7 vertebrae, and 1 rib). Lesions appeared to be more extensive on bone scans than on bone marrow scans. It was concluded that antigranulocyte bone marrow scans may show focal defects in hematopoietic bone marrow in patients with Paget's disease. Paget's disease affects the cortical bone more severely than the bone marrow.

Acute appendicitis complicating infectious mononucleosis: case report and review.

Acute appendicitis is an uncommon complication of infectious mononucleosis (IM) and can readily be misdiagnosed because of the acute abdominal pain with which patients with IM occasionally present. A case report is presented of a patient with IM who developed acute appendicitis during the acute phase of the illness. The appendicitis progressed to the formation of an abscess, which was evacuated at surgery. Histologic examination of the appendix showed absence of lymphoid follicles in the mucosal layer and intense lymphoid infiltration of the mucosa and submucosa by a mixed diffuse proliferation of lymphoid cells with groups of immunoblasts scattered among them. The lymphoid infiltrate was mainly composed of T lymphocytes; the anticomplementary immunofluorescent staining of the appendix for EBNA (Epstein-Barr nuclear antigen) was negative. Three cases of appendicitis complicating IM published in the literature are reviewed. All had clinical and histopathologic features similar to those of our patient and were cured after surgery. Our case report together with the literature review confirms that appendicitis in the acute phase of IM has distinct clinical and histopathologic features and thus has to be considered a true complication of IM rather than merely a simultaneous disease.