Comparison of the effects of denosumab with either active vitamin D or native vitamin D on bone mineral density and bone turnover markers in postmenopausal osteoporosis

Osteoporosis is a worldwide health concern. Although treatment with denosumab plus the active vitamin D alfacalcidol has been found to improve femoral neck (FN) and distal forearm bone mineral density (BMD), there have been no reports on the efficacy or adverse effects of denosumab plus eldecalcitol (ELD) in primary osteoporosis patients. Fifty-six treatment-naïve post-menopausal women with primary osteoporosis were recruited and divided into denosumab plus native vitamin D or denosumab plus ELD. Ultimately, 26 subjects in the native vitamin D group and 24 in the ELD group were analyzed. Lumbar and total hip BMD significantly increased in both groups. However, there was no significant difference in the percent increase of lumbar and total hip BMD between two groups. FN-BMD was significantly increased from 6 to 12 months in the ELD group compared with baseline. This study revealed that combination therapy with denosumab and ELD could improve FN-BMD more effectively than denosumab plus native vitamin D. Thus, the addition of ELD may enhance the effects of denosumab treatment for primary osteoporosis.     

Calcium and vitamin D in the prevention and treatment of osteoporosis - a clinical update

Combined calcium and vitamin D supplementation is an essential component of the management of osteoporosis, supported by a strong scientific rationale. The types of individuals who should receive calcium and vitamin D supplements are those: (i) patients with documented osteoporosis receiving antiresorptive or anabolic treatment; (ii) patients receiving glucocorticoids; and (iii) individuals with or at high risk of calcium and/or vitamin D insufficiencies, in particular older women and men. This article describes the evidence base that supports targeting these groups. Benefits are most apparent when 800 IU day(-1) vitamin D is complemented with a dose of 1000-1200 mg day(-1) elemental calcium. Compliance is also key to optimizing clinical efficacy.     

In whom and how to prevent glucocorticoid-induced osteoporosis

Glucocorticoid use is widespread in medicine. While it is often life-saving, side-effects are well known. The most common side-effect is osteoporosis. Today we have therapies with proven efficacy for the prevention of vertebral fractures and bone loss. Consequently recognition of glucocorticoid-induced osteoporosis is extremely important given the availability of effective therapy.     

Clinical challenges in the management of osteoporosis

While knowledge regarding the diagnosis and treatment of osteoporosis has expanded dramatically over the last few years, gaps in knowledge still exist with guidance lacking on the appropriate management of several common clinical scenarios. This article uses fictional clinical scenarios to help answer three challenging questions commonly encountered in clinical practice. The first clinical challenge is when to initiate drug therapy in a patient with low bone density. It is estimated that 34 million America have low bone density and are at a higher risk for low trauma fractures. Limitations of using bone mineral density alone for drug therapy decisions, absolute risk assessment and evidence for the cost-effectiveness of therapy in this population are presented. The second clinical challenge is the prevention and treatment of vitamin D deficiency. Appropriate definitions for vitamin D insufficiency and deficiency, the populations at risk for low vitamin, potential consequences of low vitamin D, and how to manage a patient with low vitamin D are reviewed. The third clinical challenge is how to manage a patient receiving drug therapy for osteoporosis who has been deemed a potential treatment failure. How to define treatment failure, common causes of treatment failure, and the approach to the management of a patient who is not responding to appropriate osteoporosis therapy are discussed.     

Guidelines for diagnosing,prevention and treatment of osteoporosis in Asia

According to the World Health Organization criteria, osteoporosis can be defined as a bone mineral density of −2.5 or more. Dual X‐ray densitometry is the recognised method for diagnosing osteoporosis. Drugs which have been shown to be efficacious in treating osteoporosis include alendronate, residronate, ibandronate, raloxifene, teriparitide and strontium ranleate. Patients with established osteoporosis should be treated. Primary prevention of osteoporosis is important at the community level.     

Fracture prevention strategies in patients presenting to Australian hospitals with minimal-trauma fractures: a major treatment gap

Background: The aim of this study was to examine current fracture prevention strategies through the recognition, investigation and treatment of osteoporosis in patients presenting to acute hospitals with minimal-trauma fracture.
Methods: A retrospective audit using a standardized database was conducted in 16 Australian hospitals. This involved 1829 cases of minimal-trauma fracture initially presenting to hospital emergency departments during 2003–2005. Cases of minimal-trauma fracture were retrospectively identified using diagnosis-related group fracture codes and case record review at each site. Relevant data were entered into a standardized database and analysed centrally and independently. Risk factors for osteoporosis, investigations, interventions and discharge follow up were recorded.
Results: The percentage of minimal-trauma fracture patients who underwent investigation or initiated therapy designed to prevent subsequent minimal-trauma fracture was obtained. Less than 13% of patients presenting to hospital with minimal-trauma fractures had risk factors for fracture identified. Ten per cent were appropriately investigated, 12% were commenced on calcium and 12% on vitamin D. Eight per cent started bisphosphonates and 1% selective oestrogens receptor modulators in the acute setting.
Conclusion: Most patients presenting to Australian hospitals with minimal-trauma fracture are neither investigated nor treated for osteoporosis. As this group is at high risk of subsequent fracture, this is a missed opportunity to reduce fracture burden.     

Evaluation of the efficiency of calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis: A protocol for systematic review and meta-analysis

Background:Administering corticosteroid is an effective therapeutic strategy for treating most inflammatory conditions. However, there is a chance for corticosteroid treatment to adversely affect bones, resulting in corticosteroid-induced osteoporosis, which is a highly prevalent type of secondary osteoporosis. Elevated bone resorption and reduced formation of bone are pathogenesis indicators of corticosteroid-induced osteoporosis. Preventative therapy is recommended for patients initiating steroids. This study aims to evaluate the efficiency of calcium and vitamin D in treating adults diagnosed with osteoporosis caused by corticosteroid therapy.Methods:Electronic databases will be searched systematically to source studies that have evaluated the efficiency of calcium and vitamin D as a treatment method for adult patients with osteoporosis from corticosteroid therapy. The databases include, PubMed, EMBASE, the Cochrane Library, Scopus, and Web of Science. The timeline of the search will be limited from inception to November 2020. This study will utilize the Cochrane risk of bias tool to assess the quality of the studies reviewed. Moreover, appropriate methods will be chosen to analyze the data. The RevMan 5.3 software is utilized to perform statistical analysis.Results:This study will provide additional practical and targeted results of evaluating the efficiency of calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis.Conclusion:The results of this study will provide further evidence about calcium and vitamin D in treating adults with corticosteroid-induced osteoporosis, clinicians and policymakers can make practical use of the results.Ethics and dissemination:Since this systematic review does not involve any human or animal participants, an ethics approval is not required.Systematic review registration:Aug 19, 2021. osf.io/zvb38. (https://osf.io/zvb38/).     

Denosumab‐induced hypocalcaemia in high bone turnover states of malignancy and secondary hyperparathyroidism from renal failure

Denosumab, an anti‐resorptive treatment for osteoporosis and skeletal metastases from solid tumours, can cause hypocalcaemia. The incidence may be higher than previously reported due to varying serum calcium cut‐off and timing of measurement. The following cases illustrate patients at risk of hypocalcaemia despite supplementation. These populations, with underlying high bone turnover from metastatic bone disease or secondary hyperparathyroidism due to renal failure, may require closer monitoring of calcium levels post‐denosumab administration.     

Potassium and calcium intake, excretion, and homeostasis in blacks, and their relation to blood pressure

Blacks in the United States have higher blood pressures than whites. They ingest and excrete less calcium and potassium. There is some evidence that blacks have a difference in vitamin D metabolism that might increase any problem caused by low calcium intake. Some studies can be interpreted to suggest that calcium or potassium therapy has greater hypotensive effects in blacks than in whites. Decreased intake of calcium and potassium may be major causes of the greater prevalence of hypertension in blacks than in whites. Supported by NIH, CRC Grant No. 5 MOl-RR02302.     

Herbal medications commonly used in the practice of rheumatology: mechanisms of action, efficacy, and side effects

OBJECTIVE: To review the literature on herbal preparations commonly utilized in the treatment of rheumatic indications. METHODS: Search of MEDLINE (PubMed) was performed using both the scientific and the common names of herbs. Relevant articles in English were collected from PubMed and reviewed. RESULTS: This review summarizes the efficacy and toxicities of herbal remedies used in complementary and alternative medical (CAM) therapies for rheumatologic conditions, by elucidating the immune pathways through which these preparations have antiinflammatory and/or immunomodulatory activity and providing a scientific basis for their efficacy. Gammalinolenic acid suppresses inflammation by acting as a competitive inhibitor of prostaglandin E2 and leukotrienes (LTs) and by reducing the auto-induction of interleukin1alpha (IL-1alpha)-induced pro-IL-1beta gene expression. It appears to be efficacious in rheumatoid arthritis (RA) but not for Sjogrens disease. The antiinflammatory actions of Harpagophytum procumbens is due to its action on eicosanoid biosynthesis and it may have a role in treating low back pain. While in vitro experiments with Tanacetum parthenium found inhibition of the expression of intercellular adhesion molecule-1, tumor necrosis factor alpha (TNF-alpha), interferon-gamma, IkappaB kinase, and a decrease in T-cell adhesion, to date human studies have not proven it useful in the treatment of RA. Current experience with Tripterygium wilfordii Hook F, Uncaria tomentosa, finds them to be efficacious in the treatment of RA, while Urtica diocia and willow bark extract are effective for osteoarthritis. T. wilfordii Hook F extract inhibits the production of cytokines and other mediators from mononuclear phagocytes by blocking the up-regulation of a number of proinflammatory genes, including TNF-alpha, cyclooxygenase 2 (COX-2), interferon-gamma, IL-2, prostaglandin, and iNOS. Uncaria tomentosa and Urtica diocia both decrease the production of TNF-alpha. At present there are no human studies on Ocimum spp. in rheumatic diseases. The fixed oil appears to have antihistaminic, antiserotonin, and antiprostaglandin activity. Zingiber officinale inhibits TNF-alpha, prostaglandin, and leukotriene synthesis and at present has limited efficacy in the treatment of osteoarthritis. CONCLUSIONS: Investigation of the mechanism and potential uses of CAM therapies is still in its infancy and many studies done to date are scientifically flawed. Further systematic and scientific inquiry into this topic is necessary to validate or refute the clinical claims made for CAM therapies. An understanding of the mechanism of action of CAM therapies allows physicians to counsel effectively on their proper and improper use, prevent adverse drug-drug interactions, and anticipate or appreciate toxicities. RELEVANCE: The use of CAM therapies is widespread among patients, including those with rheumatic diseases. Herbal medications are often utilized with little to no physician guidance or knowledge. An appreciation of this information will help physicians to counsel patients concerning the utility and toxicities of CAM therapies. An understanding and elucidation of the mechanisms by which CAM therapies may be efficacious can be instrumental in discovering new molecular targets in the treatment of diseases.     

Vitamin D, parathyroid hormone, and bone mineral content of lumbar spine and femur in primary biliary cirrhosis

In order to elucidate the pathogenesis and degree of osteopoenia in primary biliary cirrhosis (PBC) we conducted a cross-sectional study of 47 non-selected female patients with biopsy-proven PBC. Bone mineral content (BMC) of the lumbar spine, femoral neck and femoral shaft was determined using dual photon absorptiometry. Compared to healthy females of corresponding decades the PBC patients exhibited significantly decreased mean BMC-values in lumbar spine (88%, P less than 0.05) and femoral neck (92%, P less than 0.05) but not in femoral shaft (96%, NS). Bone mineral content was not significantly associated with duration of liver disease, impairment of liver function (serum concentrations of albumin, clotting factors II + VII + X, bilirubin, alkaline phosphatase galactose elimination capacity or histology), variables reflecting calcium homeostasis (serum concentrations of ionized calcium, parathyroid hormone, vitamin D binding protein, 25-hydroxy vitamin D3 and 1,25-dihydroxy vitamin D3) or previous treatment with glucocorticosteroids. In view of our negative findings we suggest that future studies in this field should focus on physical activity and female sex hormones as determinants for the prevention of osteopoenia in females with primary biliary cirrhosis.     

Osteoporosis after Total Gastrectomy Results of a Prospective,Clinical Study

Background: Osteopenia and enhanced risk of fractures have been reported after partial gastrectomy, but the signilicance of total gastrectomy is still unknown. Methods: Twenty-six patients were followed up for at least 3 years after total gastrectomy. The intake and S-levels of vitamin D, phosphate, magnesium, and calcium were prospectively studied, and a whole-body dual-energy X-ray absorptiometry scan was performed at a mean of 5 years after gastrectomy. Results: At this time point we found normal blood levels of vitamin D, calcium, and phosphate. Food intakes of phosphate, calcium, magnesium, and vitamin D reached the recommended daily allowances. Bone mineral density was similar to that of a control population, and increasing values were seen concomitant with an increase in body weight with the time after gastrectomy. Conclusions: Calcium homeostasis and bone mineral densities seem not to be affected by total gastrectomy, at least when studied over a period of 5 years, an observation that hypothetically can be explained by weight recovery with time after the operation.     

Secondary prevention of fractures in older people: evaluation of a protocol for the investigation and treatment of osteoporosis

It has been found previously that the investigation and treatment of osteoporosis following a fracture is poor, with only 9% of older people after a fracture being on effective osteoporosis treatment. To improve this aspect of post-fracture care in older people, a protocol has been instituted on an orthogeriatric rehabilitation ward in Christchurch, New Zealand. An audit was performed to assess the efficacy of this protocol in improving the investigation and treatment of osteoporosis (n = 193). Compliance with the investigation protocol was assessed and the pharmacological therapy initiated was requested from the general practitioner. All recommended blood-test investigations were requested in 62.8% of cases. Compared to a pre-protocol population, there was a marked increase in the measurement of bone mineral density (BMD; 93 vs 11%, P < 0.01) and vitamin D (95 vs 12%, P < 0.01). Vitamin D levels were low/-borderline in 95.6% of cases. BMD was performed in 77.7% of cases and showed osteoporosis and osteopenia to be present in 78.6 and 14.0%, respectively. For the 60 patients with BMD-confirmed osteoporosis whose therapy was obtained, 13.3% had no pharmacological therapy prescribed. Calcium, vitamin D or both were prescribed in 85.0%, bisphosphonates in 50.0% and hormone replacement therapy in 1.7% of patients. Vitamin D deficiency and osteoporosis on the basis of the BMD result are very common. The institution of a protocol has shown a significant improvement in the management of osteoporosis following a fracture. Some of the multifactorial barriers to full implementation of the guidelines are described.     

Treating osteoporosis to prevent fractures: current concepts and future developments

Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40–70%), nonvertebral (by 25–40%) and hip fractures (by 40–53%) in postmenopausal women with osteoporosis. Due to the risk of rare side‐effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well‐proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk‐based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long‐term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone‐building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better long‐term fracture prevention and should be the golden standard of future osteoporosis treatment.     

A high prevalence of hypovitaminosis D in Finnish medical in- and outpatients

OBJECTIVE: To study the prevalence of hypovitaminosis D [serum 25(OH)D < or = 37 nmol L-1)] in Finnish medical in- and outpatients in a cross-sectional study. METHODS: The subjects were 106 consecutive medical inpatients (57 females, 49 males with mean ages of 65 and 58 years) from the Peijas Hospital, Vantaa, Finland, and 99 ambulatory patients (48 females, 51 males with mean ages of 42 and 46 years) contacting a private outpatient centre in Helsinki, Finland. Serum 25(OH)D, vitamin D binding protein (DBP), free vitamin D index (FDI), intact PTH (iPTH), and albumin-corrected calcium were measured. RESULTS: Serum 25-hydroxyvitamin D [25(OH)D] was 37 nmol L(-1) or less in 70% of female and in 61% of male inpatients and in 44% of female and in 37% of male outpatients. In the whole population, a statistically significant inverse association (P < 0.0001) was detected between iPTH and 25(OH)D levels; the iPTH concentration appeared to start increasing when 25(OH)D concentration was 50 nmol L(-1) or less. The association remained the same (P < 0.0001) when FDI was used instead of 25(OH)D in the calculations. When the sexes were analysed separately, the statistically significant association was found only in females (P < 0.0001 for iPTH versus 25(OH)D; P < 0.0001 for iPTH versus FDI) but not in males. CONCLUSION: Hypovitaminosis D is very common amongst Finnish in- and outpatients in both sexes, causing secondary hyperparathyroidism in females. More extensive studies are warranted to elucidate the vitamin D status of the Finnish population.     

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维生素D缺乏所致的儿童佝偻病和成年后骨软化会促发并加重年老后发生的骨量减少或骨质疏松。因此,充足的维生素D是保证有效预防和治疗骨质疏松的基础。反映体内维生素D水平的最佳指标是血清25-羟维生素D[25(OH)D],其水平与骨密度、骨折风险和跌倒风险呈负相关。最优化的25(OH)D范围为30~50μg/L,20~<30μg/L为不足,低于20μg/L为缺乏。推荐老年人每天补充800~1000 U普通维生素D,骨质疏松患者、肥胖、缺乏日照和吸收不良的人可酌情增加至2000 U。