Patterns of Osteoporosis Medications Selection After Drug Holiday or Continued Therapy: A Real-World Experience

ObjectivePublished literature on physicians’ preferences and sequential treatment patterns of osteoporosis therapy is scarce.MethodsA retrospective cohort study of patients who received bisphosphonates, denosumab, and/or raloxifene for at least 3 consecutive years or teriparatide for at least 18 months for osteoporosis. Data collection spanned 10 years, from October 2007 to September 2016, at a tertiary care center in the United States.ResultsIn total, 12 885 patients were identified on the basis of receiving at least 1 treatment at any point in time; 1814 patients were randomly reviewed, and 274 patients met the inclusion criteria. The mean age was 68.8 ± 10.7 years, and women represented 90.9% of all the cases. Primary care physicians and rheumatologists constituted 65.7% and 22.6% of the prescribers, respectively. Before instituting a drug holiday, alendronate was the most common initial treatment (percentage, mean duration ± standard deviation in years: 69%, 5.4 ± 2.4 years) followed by ibandronate (9.5%, 4.9 ± 2.1 years) and raloxifene (9.1%, 5.2 ± 1.6 years). Denosumab was the most common second course of treatment, accounting for 29.3% of 82 patients who were subsequently prescribed another therapy, followed by alendronate (24.4%) and zoledronate (20.7%). Among patients who were placed on a drug holiday and eventually restarted on osteoporosis therapy, denosumab was the most common treatment instituted (n = 21), accounting for 40% of the total patients, followed by alendronate (32%) and zoledronate (16%). There was a progressive decline in osteoporosis therapy over the duration of the study.ConclusionAlendronate was the most common initial therapy. Denosumab was the most common second course of treatment prescribed.     

蚌埠市蚌山区老年人群骨质疏松症流行病学调查及对跌倒风险和认知功能的影响

摘要 目的：对蚌埠市蚌山区老年人群骨质疏松症进行流行病学调查,并探讨骨质疏松症对跌倒风险和认知功能的影响。方法：于2019年11月~2021年4月采用多阶段分层随机抽样的方法,抽取蚌埠市蚌山区的常住居民,调查老年人群骨质疏松症发生率,共发放960份调查问卷,回收941份,回收率为98.02%。根据有无骨质疏松症分为骨质疏松症组和无骨质疏松症组,观察两组跌倒风险和认知功能状况。应用多因素logistic回归分析老年人群发生骨质疏松症的危险因素和保护因素。结果：941例研究对象中,检查出存在骨质疏松症者325人,发病率为34.54%。根据有无骨质疏松症分为骨质疏松症组（n=325）和无骨质疏松症组（n=616）。单因素分析结果显示,老年人群发生骨质疏松症与乳制品和钙片摄入情况、年龄、连续服用类固醇激素超过3个月情况、骨折史、性别、其他慢性病患病情况、体质量指数、婚姻状况、饮茶情况、每天运动情况有关（P<0.05）。多因素logistic回归性分析,结果显示：年龄≥70岁、性别为女性、连续服用类固醇激素超过3个月情况是老年人群发生骨质疏松症的危险因素,而每天运动情况≥30 min、有乳制品和钙片摄入情况、体质量指数≥24 kg/m²是老年人群发生骨质疏松症的保护因素（P<0.05）。骨质疏松症组的跌倒风险评估工具（FROP-Com）评分高于无骨质疏松症组,跌倒效能量表（MFES）评分低于无骨质疏松症组（P<0.05）。骨质疏松症组的简明精神状态检查量表（MMSE）评分低于无骨质疏松症组,画钟试验（CDT）评分高于无骨质疏松症组（P<0.05）。结论：蚌埠市蚌山区老年人群骨质疏松症患病率较高,且受到年龄、性别、连续服用类固醇激素超过3个月情况等因素的影响,而每天运动情况≥30 min、乳制品和钙片摄入情况、体质量指数≥24 kg/m²可减少骨质疏松症患病率,同时存在骨质疏松症的患者其跌倒风险升高,认知功能下降。     

Reduction of lecithin-cholesterol acyltransferase, apolipoprotein D and the Lp(a) lipoprotein with the anabolic steroid stanozolol

The effects of the anabolic steroid stanozolol (17-methyl-2H-5 alpha-androst-2-eno-(3,2-c)pyrazol-17 beta-ol) on lecithin-cholesterol acyltransferase, apolipoproteins B and D and the Lp(a) lipoprotein were determined in a prospective study of ten normolipidemic women with postmenopausal osteoporosis. Lecithin-cholesterol acyltransferase was reduced approx. 30% by 6 weeks of treatment with stanozolol (off treatment 5.1 +/- 1.2, on treatment 3.4 +/- 0.8 muml; P less than 0.02). The Lp(a) lipoprotein was reduced 65 +/- 23% by the steroid treatment (off treatment 5.5 +/- 5.5, on treatment 1.4 +/- 0.7 mg/dl; P less than 0.02). Apolipoprotein D was reduced 23 +/- 9% by the treatment (off treatment 5.9 +/- 0.9, on treatment 4.5 +/- 0.7 mg/dl; P less than 0.02). In contrast, apolipoprotein B increased slightly but insignificantly on steroid therapy (off treatment 90 +/- 21, on treatment 112 +/- 24 mg/dl). By 5 weeks after the drug was discontinued, all four of these proteins were near pretreatment levels. These significant changes in lipoprotein metabolism, combined with our previous report of reductions of HDL and particularly HDL2, suggest the need for caution in the long-term use of anabolic steroids.     

Prevalence of xerostomia and hyposalivation in the nursing home and the relation with number of prescribed medication

In nursing homes, the number of patients with their own dentition increases. Many of them, however, are unable to perform oral hygiene procedures. Medication is considered to be an important cause of hyposalivation, which may lead to oral alterations and loss of teeth. The aim of the present study was to investigate the prevalence of xerostomia and hyposalivation in a Dutch nursing home and to examine the possible relation with medication usage. Between January and March 2001, the salivary flow rates were measured in 50 patients residing in a nursing home in Amsterdam. Unstimulated saliva, parafilm-stimulated saliva and citric acid stimulated saliva were determined. Xerostomia was determined by the question "My mouth feels dry" and the medication used was examined. The data were analysed with (M)ANOVA. The average age of the patients was 78.1 +/- 9.7 years. Forty-eight % of the patients had an unstimulated flow rate of less then 0.20 ml/min and 24% had a flow rate even lower than 0.10 ml/min (reference values: 0.25-0.50 ml/min). The flow rate of women was significantly lower than that of men (p < 0.01), even after correction for age, smoking and the number of prescribed medications. Salivary flow rates decreased significantly with age (p < 0.05). The number of prescribed medication was significantly higher in patients over the age of 70 (p < 0.01, n = 42) and also in women (p < 0.01). The prevalence of xerostomia was 52% with no difference between men and women. In nursing homes, the prevalence of hyposalivation and xerostomia is high. The number of xerogenic medications used seems to be an important factor. Women and patients aged over the age of 70 years need special attention with respect to oral health.     

The prospective evaluation of the osteoporotic vertebral fractures incidence in a random population sample

Introduction Osteoporotic vertebral fractures are mostly incidental but in some patients may lead to clinical symptoms, characteristic deformations of the vertebral column and increase total mortality. The aim of the study was to evaluate the prevalence of osteoporotic vertebral fractures and risk factors for osteoporosis in a random sample of Szczecin inhabitants aged over 50 in the relation to the whole European population examined in the frame of EVOS (European Vertebral Osteoporosis Study) and its prospective phase - EPOS (European Prospective Osteoporosis Study). At the baseline, 607 persons were studied, including 301 women and 306 men. Material and methods The questionnaire on the risk factors for osteoporosis and the spine X-rays analysed by morphometry, were taken in all subjects. The incidence of osteoporotic vertebral deformity in the studied population was similar in both sexes (12.6% women and 10,3% men) but in men aged 50-64 fracture incidence was significantly higher in comparison with women. The prevalence of new vertebral fractures examined after 4 years was higher in women than in men (9.1 vs 6.4/1000 persons years). Among the risk factors for osteoporosis, low physical activity and prolonged immobilization in women significantly influenced the incidence of vertebral deformities. Conclusions: 1) The study shows the high incidence of risk factors and osteoporotic vertebral deformities in the population of Szczecin inhabitants aged over 50. 2) Visual assessment only with a combination with morphometry is an optimal tool for detection of incident vertebral fractures.     

PAGET'S DISEASE—Changes Occurring Following Treatment with Newer Hormonal Agents

From experience in six cases the anabolic steroid hormones, especially long-acting testosterone and estrogen preparations, are the treatment of choice in Paget''s disease, as in postmenopausal osteoporosis. Details of the management of three patients over a period of four years are presented.Roughly 4 per cent of the population, mostly persons over 40, show some evidence of Paget''s disease. Only a small number of them, however, have severe manifestations requiring treatment, such as pain, howing or fracture of the bones, pressure on nerves or heart failure. In rare cases malignant changes occur in the involved bone.Since the cause of Paget''s disease is not known, treatment in the past has been largely empirical. Reifenstein and Albright had advocated the therapeutic use of calcium, vitamin D and ascorbic acid, and, in postmenopausal women, administration of estrogens; but with fractures or immobilization, intake of calcium-containing foods, such as milk, must be restricted to avoid dangerous piling up of calcium and kidney stones, and fluids must be forced. In recent years anabolic steroid hormones, principally oral androgens and estrogens, have been employed by Gordan and others to promote bone repair, lessen bone pain and decrease urinary excretion of calcium. While these hormones probably do not arrest the disease, they seem to stabilize it and bring relief of symptoms.More recently, Albright and Henneman demonstrated that very large doses of corticotropin (ACTH) or cortisone resulted in immediate cessation of bone pain, decrease in urinary excretion of calcium and histologic evidence of regression of the disease process. The large doses required, however, also produce dangerous side effects, such as psychosis and osteoporosis, indicating that such treatment probably should not be continued over long periods.     

Evidence for efficacy of drugs affecting bone metabolism in preventing hip fracture.

OBJECTIVE--To examine the effects of taking drugs affecting bone metabolism on the risk of hip fracture in women aged over 50 years. DESIGN--Retrospective, population based, case-control study by questionnaire. SETTING--14 centres in six countries in southern Europe. SUBJECTS--2086 women with hip fracture and 3532 control women matched for age. MAIN OUTCOME MEASURES--Number of drugs affecting bone metabolism taken and length taken for. RESULTS--Women taking drugs affecting bone metabolism had a significantly decreased risk of hip fracture. After adjustment for differences in other risk factors, the relative risk of hip fractures was 0.55 (95% confidence interval 0.31 to 0.85) in women taking oestrogens, 0.75 (0.60 to 0.94) in those taking calcium, and 0.69 (0.51 to 0.92) in those taking calcitonin. The fall in risk was not significant for anabolic steroids (0.6 (0.29 to 1.22)). Neither vitamin D nor fluorides were associated with a significant decrease in the risk of hip fracture. The effect on hip fracture risk increased significantly with increasing duration of exposure (risk ratio 0.8 (0.61 to 1.05) for less than median exposure v 0.66 (0.5 to 0.88) for greater than median exposure). Drugs were equally effective in older and younger women, with the exception of oestrogen. CONCLUSIONS--Oestrogen, calcium, and calcitonins significantly decrease the risk of hip fracture. Short term intervention late in the natural course of osteoporosis may have significant effects on the incidence of hip fracture.     

Current indications for prevention and therapy of steroid-induced osteoporosis in men and women

Steroid-induced osteoporosis is a textbook example of the secondary type of this medical condition. Glucocorticosteroids suppress bone formation by their direct and indirect effect on osteoblasts, osteoclasts and osteocytes, increasing their resorption and, eventually, leading to negative bone balance. A clinical problem arises regarding the fact that approximately 50% of patients on chronic steroid therapy undergo asymptomatic bone fractures. The treatment mode includes minimising the dose of administered steroids, encouraging an improved lifestyle and supplementation with adequate calcium and vitamin D(3) doses. Bisphosphonates are a group of medical agents used both to prevent and treat steroid-induced osteoporosis, although new therapies have also become available in recent years.     

Skeletal effects of oral oestrogen compared with subcutaneous oestrogen and testosterone in postmenopausal women.

STUDY OBJECTIVE--To compare oral and implanted oestrogens for their effects in preventing postmenopausal osteoporosis. DESIGN--Non-randomised cohort study of postmenopausal women treated with oral or depot oestrogens and postmenopausal controls. SETTING--Gynaecological endocrine clinic in tertiary referral centre. PATIENTS--Oral treatment group of 37 postmenopausal women (mean age 57.5 years, median 8.75 years from last menstrual period), compared with 41 women given oestrogen implants (mean age 56.2 years, median 9.5 years from last menstrual period) and 36 controls (mean age 51.8 years, median 2.0 years from last menstrual period). Weight was not significantly different among the groups. INTERVENTIONS--Oral treatment group was given continuous treatment with cyclic oestrogen and progesterone preparations (Prempak C or Cycloprogynova) for a median of 8.0 years. Implant group was given subcutaneous implants of oestradiol 50 mg combined with testosterone 100 mg, on average six monthly for a median of 8.5 years. Controls were not treated. END POINT--Significant increase in bone density. MEASUREMENTS AND MAIN RESULTS--Bone density measured by dual beam photon absorptiometry was 1.02 (SD 0.13) g hydroxyapatite/cm2 in implant group versus 0.89 (0.11) in oral group (p less than 0.01) and 0.87 (0.14) in controls (p less than 0.01). Serum oestradiol concentration in implant group was (median) 725 pmol/l versus 170 pmol/l in oral group (p less than 0.01) and 99 pmol/l in controls (p less than 0.01). Serum follicular stimulating hormone was median 1 IU/l (range 1-11) in implant group (equivalent to premenopausal values) versus 43 (4-94) IU/l in oral group (p less than 0.01) and 72 (28-99) IU/l in controls (p less than 0.01). CONCLUSIONS--Subcutaneous oestrogen is more effective than oral oestrogen in preventing osteoporosis, probably owing to the more physiological (premenopausal) serum oestradiol concentrations achieved. It also avoids problems of compliance that occur with oral treatment.     

Sex chromatin in women treated with steroid hormones

3 groups of women, aged 15-71 years, were examined: a control group of 17 healthy women and 11 women with blood complications who had nver received steroid treatments, a 2nd group of patients with complications similar to the 1st groups' who were treated with the steroid preparation Enkorton-Polfa (for 5-10 days at 20-50 mg daily), and a 3rd group of 20 patients with similar prolonged complciations from 4 weeks to 5 years) who were treated with the steroid preparation Enkorton-Polfa in daily doses of 10-160 mg. Sex chromatin from these 3 groups was studied using the method of Sanderson and Stewart and the results compared. A lower percentage of sex chromatin bodies was found in those treated with steroids. Significant statistical differences were found in the comparison of the standard deviations of sex chromatin count: Group 1, + or -13%; Group 2, + or -10% before treatment and + or -5% during treatment; and Group 3, + or -8%.     

Negative impact of Crohn's disease on bone mineral mass

Prolonged chronic inflammation and corticosteroid therapy increase the risk of osteoporosis in patients with Crohn's disease. It has been estimated that 30% of these patients, who take steroids for prolonged periods, will suffer a vertebral fracture. Patients with Crohn's disease are difficult to wean from corticosteroids and therefore are at risk of developing bone complications. The purpose of this cross-sectional study was to examine the relationship between cumulative steroid dose, duration of the disease and the development of osteopenia in patients with Crohn's disease. We studied 28 patients (17 men, 11 women) with Crohn's disease: eight had one or more bowel resections and all the women were premenopausal. Serum calcium, phosphate, total alkaline phosphatase, immunoreactive parathyroid hormone (iPTH), 25(OH)Vitamin D(3) and 1,25 (OH)(2) Vitamin D(3) were measured by autoanalyser methods or radioimmunoassay. Bone mineral density (BMD) was studied using dual energy X-ray bone absorptiometry of the lumbar spine (L2-L4) and the femoral neck. Of these 28 patients, 27 received an average of 17.3 +/- 21.7 g (range 1 to 80) g of prednisone over a period of 4 to 216 months. Fourteen out of the 28 patients had mildly diminished bone density (z-score >-2.5 SD and < -1 SD) of the spine and 15/28 of the hip. We found a greater decrease in bone density (z-score < -2.5 SD) in 2 out of 28 patients at the spine and in 5 out of 28 at the femoral neck. Those in whom the duration of the disease was less than two years (12 patients) had significantly higher vertebral z-scores (-0.096 +/-0.91) than those who had the disease for over two years (-1.31 +/- 2.37), (p<0.05). We found no significant correlation between lumbar spine and femoral neck z-scores and cumulative steroid therapy. Six out of 28 patients (four women and two men), of mean age 47.2+/-11.7, had one vertebral fracture. The mean cumulative dose of steroids (prednisone or budesonide) in patients with vertebral fractures was higher but not significantly different from that in patients without fractures -20.1+/-18.2 versus 14.1+/-11.2 g of prednisone, respectively (p>0.05). No correlation was found between various serum hormones and other biochemical parameters of bone turnover or bone density. We conclude that a large proportion of patients with Crohn's disease have reduced bone mineral density (58% at the spine and 75% at the femoral neck). The pathogenesis of bone loss is probably multifactorial. Although steroid therapy might be an important contributory factor, we were unable to find a significant correlation between it and bone loss. On the contrary, we observed that the duration of the disease makes a significant contribution to bone loss.     

Prospective double-blind trial of synthetic steroid (Org OD 14) for preventing postmenopausal osteoporosis.

A double-blind trial of Org OD 14, a synthetic steroid with an unusual endocrine profile, was conducted on 100 postmenopausal women; of these, 63 completed two years'' treatment (33 Org OD 14; 30 placebo). A dose of 2.5 mg/day successfully prevented bone loss over two years, whereas a significant reduction in bone mineral content occurred in women taking placebo, the rate being comparable to that in earlier studies (p less than 0.01). At the dosage used (2.5 mg/day) Org OD 14 also significantly reduced the severity of menopausal complaints (flushing, sweating, etc). Vabra aspiration curettage in 20 cases 6-18 months after starting active treatment showed no evidence of endometrial hyperplasia, though weak proliferation of the endometrium was seen in three. Org OD 14 may provide a new approach to hormonal prevention of bone loss in postmenopausal women without inducing appreciable endometrial stimulation; the potential value of Org OD 14 in osteoporosis and other post-climacteric complaints warrants further investigation.     

Patterns of Anti-Osteoporosis Medication Use among Women at High Risk of Fracture: Findings from the Global Longitudinal Study of Osteoporosis in Women (GLOW)

Objective

To assess patterns of anti-osteoporosis medication (AOM) use over 3 years among women at high risk of major fracture.

Methods

The GLOW registry follows a cohort of more than 40,000 women aged ≥55 from 615 primary care practices in 10 countries. Self-administered surveys (baseline, 12, 24, and 36 months) collected data on patient characteristics, perception of fracture risk, and AOM use. FRAX scores were calculated from the baseline surveys and women classified as high risk if their FRAX 10-year probability of major fracture was ≥20%.

Results

A total of 5774 women were classified as at high risk and had complete data over 3 years. At baseline, 2271 (39%) reported receiving AOM, 739 (13%) reported prior but not current use, and 2764 (48%) said they had never used AOM. Over 3 years, 85% of baseline non-users continued as non-users and 15% initiated AOM; among baseline users, 49% continued the same medication class, 29% stopped AOM, and 12% switched. Women who stopped AOM were less likely to self-report osteoporosis (HR 0.56, 95% CI 0.42–0.75) than women who continued AOM. Compared with non-users who did not begin treatment, women initiating AOM were more likely to report a diagnosis of osteoporosis (HR 11.3, 95% CI 8.2–15.5) or osteopenia (HR 4.1, 95% CI 2.9–5.7) and be very concerned about osteoporosis (HR 1.9, 95% CI 1.3–2.8).

Conclusions

Less than 40% of women at high risk of fracture reported taking AOM. Women who stopped AOM were less likely to believe they have osteoporosis. Women who initiated treatment appeared motivated primarily by a diagnosis of osteoporosis or osteopenia and concern about the condition.     

Current indications for prevention and therapy of steroid-iduced osteoporosis in men and women

Steroid-induced osteoporosis is a textbook example of the secondary type of this medical condition. Glucocorticosteroids suppress bone formation by their direct and indirect effect on osteoblasts, osteoclasts and osteocytes, increasing their resorption and, eventually, leading to negative bone balance. A clinical problem arises regarding the fact that approximately 50% of patients on chronic steroid therapy undergo asymptomatic bone fractures. The treatment mode includes minimising the dose of administered steroids, encouraging an improved lifestyle and supplementation with adequate calcium and vitamin D3 doses. Bisphosphonates are a group of medical agents used both to prevent and treat steroid-induced osteoporosis, although new therapies have also become available in recent years.