Zoledronic Acid Once-yearly: What Role in the Prevention of Non-vertebral Osteoporotic Fractures?

Osteoporosis is the most common bone disease. Low levels of oestrogens or testosterone are risk factors for primary osteoporosis. The most common cause of secondary osteoporosis is glucocorticoid treatment, but there are many other secondary causes of osteoporosis. Osteoporosis can be secondary to anti-oestrogen treatment for hormone-sensitive breast cancer and to androgen-deprivation therapy for prostate cancer. Zoledronic acid is the most potent bisphosphonate at inhibiting bone resorption. In osteoporosis, zoledronic acid increases bone mineral density for at least a year after a single intravenous administration. The efficacy and safety of extended release (once-yearly) zoledronic acid in the treatment of osteoporosis is reviewed.

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Romosozumab: A first-in-class sclerostin inhibitor for osteoporosis

American Journal of Health-System Pharmacy ◽

10.1093/ajhp/zxaa285 ◽

2020 ◽

Vol 77 (23) ◽

pp. 1949-1956

Author(s):

Caitlin Prather ◽

Erin Adams ◽

Whitney Zentgraf

Keyword(s):

Clinical Trials ◽

High Risk ◽

Bone Resorption ◽

Bone Formation ◽

English Language ◽

Safety Concern ◽

Osteoporotic Fractures ◽

Mineral Density ◽

Treatment Of Osteoporosis ◽

Poster Presentations

Abstract Purpose The purpose of this article is to review the pharmacology, efficacy, and safety of the sclerostin inhibitor romosozumab for the treatment of osteoporosis, including data from clinical trials of the drug. Summary A review of the literature was performed by searching PubMed and MEDLINE for all relevant articles published between January 2014 and February 2020 using the keywords romosozumab, romosozumab-aqqg, osteoporosis, and fracture. All relevant English-language articles evaluating the pharmacology, efficacy, or safety of romosozumab for the treatment of osteoporosis in humans were included; poster presentations were excluded. Romosozumab has been approved by the Food and Drug Administration and is considered both safe and effective for the treatment of osteoporosis in high-risk postmenopausal females. Phase 2 and phase 3 clinical trials have shown a statistically significant decrease in new vertebral fractures and an increase in bone mineral density with romosozumab use, as compared with both placebo use and use of alternative osteoporosis therapies. The primary safety concern is a potential risk of cardiovascular events; additionally, hypocalcemia must be corrected prior to initiation. Romosozumab is the first anabolic medication that both increases bone formation and decreases bone resorption. Data suggest that romosozumab is more effective than oral bisphosphonates in preventing osteoporotic fractures, though cost and safety concerns must be considered. Conclusion Romosozumab is a novel, 12-month treatment option for postmenopausal women at high risk for osteoporotic fracture that both increases bone formation and decreases bone resorption.

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Prevalence and incidence of osteoporotic fractures in patients on long-term glucocorticoid treatment for rheumatic diseases: the Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) study

Reumatismo ◽

10.4081/reumatismo.2017.922 ◽

2017 ◽

Vol 69 (1) ◽

pp. 30 ◽

Cited By ~ 12

Author(s):

M. Rossini ◽

O. Viapiana ◽

M. Vitiello ◽

N. Malavolta ◽

G. La Montagna ◽

...

Keyword(s):

Risk Factors ◽

Vertebral Fractures ◽

Chronic Treatment ◽

Randomized Clinical Trials ◽

Real Life ◽

Connective Tissue Diseases ◽

Specific Treatment ◽

Osteoporotic Fractures ◽

Mineral Density ◽

Glucocorticoid Treatment

Osteoporosis and fractures are common and invalidating consequences of chronic glucorticoid (GC) treatment. Reliable information regarding the epidemiology of GC induced osteoporosis (GIOP) comes exclusively from the placebo group of randomized clinical trials while observational studies are generally lacking data on the real prevalence of vertebral fractures, GC dosage and primary diagnosis. The objective of this study was to evaluate the prevalence and incidence of osteoporotic fractures and to identify their major determinants (primary disease, GC dosage, bone mineral density, risk factors, specific treatment for GIOP) in a large cohort of consecutive patients aged >21 years, on chronic treatment with GC (≥5 mg prednisone - PN - equivalent) and attending rheumatology centers located all over Italy. Glucocorticoid Induced OsTeoporosis TOol (GIOTTO) is a national multicenter cross-sectional and longitudinal observational study. 553 patients suffering from Rheumatoid Arthritis (RA), Polymyalgia Rheumatica (PMR) and Connective Tissue Diseases (CTDs) and in chronic treatment with GCs were enrolled. Osteoporotic BMD values (T score <-2.5) were observed in 28%, 38% and 35% of patients with CTDs, PMR or RA at the lumbar spine, and in 18%, 29% and 26% at the femoral neck, respectively. Before GC treatment, prevalent clinical fractures were reported by 12%, 37% and 17% of patients with CTDs, PMR, or RA, respectively. New clinical fragility fractures during GC treatment were reported by 12%, 10% and 23% of CTDs, PMR and RA patients, respectively. Vertebral fractures were the prevailing type of fragility fracture. More than 30% of patients had recurrence of fracture. An average of 80% of patients were in supplementation with calcium and/or vitamin D during treatment with GCs. Respectively, 64%, 80%, and 72% of the CTDs, PMR and RA patients were on pharmacological treatment for GIOP, almost exclusively with bisphosphonates. The GIOTTO study might provide relevant contributions to clinical practice, in particular by highlighting and quantifying in real life the prevalence of GIOP and relative fractures, the frequency of the main risk factors, and the currently sub-optimal prevention. Moreover, these results emphasize the importance of the underlying rheumatic disease on the risk of GIOP associated fractures.

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Analysis of adherence to treatment of patients with osteoporosis in the Omsk region (based on materials from the regional Center for the prevention and treatment of osteoporosis

Osteoporosis and Bone Diseases ◽

10.14341/osteo12695 ◽

2021 ◽

Vol 23 (3) ◽

pp. 17-23

Author(s):

Elena A. Vilms ◽

Evgeniya V. Dobrovolskaya ◽

Maria S. Turchaninova ◽

Elena A. Bykova

Keyword(s):

Comparative Analysis ◽

Zoledronic Acid ◽

Chronic Conditions ◽

Clinical Medicine ◽

Osteoporotic Fractures ◽

Adherence To Treatment ◽

Treatment Of Osteoporosis ◽

Regional Center ◽

Prevention And Treatment

Background. Non-adherence to treatment, especially in chronic conditions, is a significant problem facing clinical medicine. Failure to adhere to treatment recommendations is often noted in the treatment of osteoporosis, which reduces the effectiveness of anti-osteoporotic drugs and a set of measures to prevent the occurrence of osteoporotic fractures.Aim. The aim of the study was to assess the adherence of patients of the Center for the Prevention and Treatment of Osteoporosis to treatment with anti-osteoporotic drugs of pathogenetic action.Materials and methods. This continuous observational study analyzed the adherence to long-term anti-osteoporotic therapy of patients observed at the Center for the Prevention and Treatment of Osteoporosis, the reasons for discontinuing treatment, doctors’ preferences in prescribing anti-osteoporotic therapy, reasons for changing the anti-osteoporotic drug. The study period is from July to December 2019.Results. During the analyzed period, 625 patients turned to the Center for the Prevention and Treatment of Osteoporosis. The preferences of doctors when prescribing anti-osteoporotic therapy have changed: the proportion of prescriptions for zoledronic acid and denosumab increased, mainly due to a reduction in the prescriptions of strontium ranelate, as well as risendronic acid, teriparatide, and calcitonin was no longer prescribed. Among 370 patients who received a therapeutic appointment (with an already known outcome of a therapeutic appointment), 40.0 ± 2.5% were non-compliant. Including: 9.7 ± 1.5% did not start taking the drug, interrupted the course ahead of schedule — 28.7 ± 2.4%. The termination of the course of therapy in 57.7% of cases was unauthorized, in another 42.3% it was associated with side effects. Patients started and continued further therapy with the initially prescribed drug in 53.8% of cases. As expected, the best adherence rates were found for drugs with parenteral administration once a year (zoledronic acid).Conclusions. Comparative analysis of the prescriptions of the main drugs of the pathogenetic action of patients of the center for the prevention and treatment of osteoporosis showed low compliance.

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STUDY OF INCIDENCE OF OSTEOPOROSIS INDUCED FRACTURES IN THE ELDERLY AFTER ONCE YEARLY ZOLEDRONIC ACID INJECTION

10.36106/ijsr/9601740 ◽

2021 ◽

pp. 1-2

Author(s):

Raveendra Babu. Rayalapeta. Veerappa ◽

Achyuth Babu. Rayalapeta Bodan

Keyword(s):

Developing Countries ◽

Placebo Group ◽

Zoledronic Acid ◽

Rural Areas ◽

Osteoporotic Fractures ◽

The Elderly ◽

Mineral Density ◽

Distal Radial Fractures ◽

Neck Of Femur ◽

Study Results

Introduction: In developing countries like India, the various socio-economic factors like anaemia, hypo proteinemia, early menopause, hysterectomy at younger age and loss of teeth at early age are leading causes of osteoporosis. The treatment for all the above problems at community level is difficult job. We advocated IV injections of Zoledronic acid once in a year which is feasible and possible way of preventing the progression of osteoporosis. This is evidenced by decrease in incidence of new fractures in our patients. Patients and Methods: We studied the efficacy of once yearly IV injection of Zoledronic acid -ZOLE to prevent osteoporotic fractures in the 130 elderly patients and compared the incidence of fractures in the placebo group of 150 patients who were not received the ZOLE injection. The age group ranges from 50 to 70 years who attended OP unit of our Orthopaedic department from January 2018 to December 2019 (2 years). These 280 patients presented with common fractures like fracture neck of femur-110, vertebral fractures-85, proximal tibial fractures-15, proximal humoral fractures-15 and distal radial fractures-55. IV Zoledronic acid was given to 130 patients in addition to fracture treatment. The remaining 150 patients who were not willing for IV injections for various reasons were included in the placebo group of our study. Results: We assessed the incidence of new fractures in both the groups patients, ZOLE group who received Zoledronic injection and placebo group who were not received injection for 2 years period. The incidence of new fractures was significantly diminished in ZOLE group compared to placebo group. We observed the incidence of all cumulative fractures were 30 fractures (24%) in the ZOLE group and in the placebo group the incidence was 110 fractures (76%). Bone mineral density (BMD) of Lumbar spine, femoral neck, proximal humerus and distal radius were done for all the patients at the time of starting of the study and at 2 years follow-up. We observed increased BMD in the ZOLE group. There were no adverse effects like osteonecrosis of jaw and others in our study. Conclusion: In rural areas of developing countries, with poor socioeconomic status, early osteoporosis is prevalent and causing the major fractures after trivial injury. Once yearly administration of Zoledronic acid 5 mg IV is safe and effective way of preventing the incidence of Fractures and subsequent morbidity and mortality.

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Zoledronic acid versus placebo in pediatric glucocorticoid-induced osteoporosis: A randomized double-blind phase 3 trial

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgab458 ◽

2021 ◽

Author(s):

Leanne M Ward ◽

Anup Choudhury ◽

Nathalie Alos ◽

David A Cabral ◽

Celia Rodd ◽

...

Keyword(s):

Zoledronic Acid ◽

Least Squares ◽

Osteoporotic Fractures ◽

Z Score ◽

Mineral Density ◽

Phase 3 ◽

Double Blind ◽

Acid Versus ◽

One Year ◽

Pediatric Illnesses

Abstract Context Glucocorticoids (GC) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures. Objective To determine the efficacy and safety of intravenous (IV) zoledronic acid (ZA) compared with placebo to treat pediatric GC-induced osteoporosis (GIO). Patients, Design and Setting Children 5-17 years of age with GIO were enrolled in this multi-national randomized, double-blind, placebo-controlled phase 3 trial (ClinicaTrials.gov NCT 00799266). Interventions and Main Outcome Measures Eligible children were randomized 1:1 to six monthly IV ZA 0.05 mg/kg or IV placebo. The primary endpoint was the change in lumbar spine bone mineral density Z-score (LSBMDZ) from baseline to month 12. Incident fractures and safety were assessed. Results Thirty-four children were enrolled (mean age 12.6 ± 3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures. LSBMDZ increased from −2.13 ± 0.79 to −1.49 ± 1.05 on ZA, compared with −2.38 ± 0.90 to −2.27 ± 1.03 on placebo (least squares means difference 0.41 [95% confidence interval 0.02, 0.81; p=0.04]); when corrected for height Z-score, the least squares means difference in LBMDZ was 0.75 [0.27, 1.22; p=0.004]. Two children on placebo had new low-trauma VF versus none on ZA. Adverse events (AEs) were reported in 15/18 children (83%) on ZA, and in 12/16 (75%) on placebo, most frequently within 10 days after the first infusion. There were no deaths, nor treatment discontinuations due to treatment-emergent AEs. Conclusions LSBMDZ increased significantly on ZA compared with placebo over one year in children with GIO. Most AEs occurred after the first infusion.

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Use of teriparatide in treatment of severe osteoporosis in geriatric practice: a clinical case review

Obesity and metabolism ◽

10.14341/omet10052 ◽

2020 ◽

Vol 16 (4) ◽

pp. 80-89

Author(s):

Ekaterina N. Dudinskaya ◽

Olga N. Tkacheva ◽

Liubov V. Machekhina ◽

Valentina S. Ostapenko ◽

Natalya V. Brailova

Keyword(s):

Clinical Case ◽

Osteoporotic Fractures ◽

Case Review ◽

Mineral Density ◽

Severe Osteoporosis ◽

Treatment Of Osteoporosis ◽

Drug Of Choice ◽

Age Related ◽

Risk Of Falls ◽

Anabolic Therapy

Elderly and senile people are characterized by a high prevalence of osteoporosis, which, in turn, increases the risk of fractures, including the repeated ones. Fractures in osteoporosis are an extremely unfavorable complication of the disease, leading to catastrophic consequences in old age. The prevalence of osteoporotic fractures progressively increases with age. At present, the cumulative frequency of hip fractures in women over 80 is about 30%. The proportion of vertebral fractures in women older than 80 years is up to 40% of all vertebral osteoporotic fractures. Despite the tremendous successes achieved in the diagnosis and treatment of osteoporosis, the disease itself and related fractures remain a serious medical, economic and social problem. Prevention of recurrent fractures in geriatric patients is a system of preventive, rehabilitative and therapeutic measures aimed at reducing the risk of falls, choosing an effective therapy, and reducing the risk of recurring fractures. A serious problem in the treatment of osteoporosis in older people is the inefficiency of the antiresorptive therapy due to an age-related decrease in bone formation. There are frequent cases of a continuing decrease in bone density, the occurrence of repeated fractures during ongoing therapy of osteoporosis. Often the therapy of choice in this case is bone-anabolic therapy with teriparatide, which allows one to achieve good results in the accumulation of bone mineral density. In this article, we will present the clinical case of an elderly patient with severe osteoporosis, in which teriparatide became the drug of choice.

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Role of zoledronic acid in treatment of osteoporosis and prevention of fractures

Medical Council ◽

10.21518/2079-701x-2021-21-2-102-109 ◽

2022 ◽

pp. 102-109

Author(s):

A. V. Krivova ◽

V. P. Zakharov ◽

A. N. Sharov

Keyword(s):

Quality Of Life ◽

Zoledronic Acid ◽

Mineral Density ◽

Treatment Of Osteoporosis ◽

Vertebral Body Fractures ◽

Bone Deficiency ◽

Minimal Trauma ◽

Primary Disability ◽

Pharmacological Correction

Introduction. One of the causes of primary disability and high mortality, among patients with osteoporosis, are fractures that occur with minimal trauma, as a rule, it is a fall from the height of one’s own height. The final link in the chain of preventive measures to reduce the frequency of osteoporosis and fractures on its background is the introduction of pharmacological correction of bone deficiency into the practical activity of an orthopedic traumatologist. Currently, there are several drugs that can change the disturbed metabolism. For example, the use of zoledronic acid significantly reduces the risk of fractures.Aim: to study the effect of zoledronic acid on bone mineral density in patients with osteoporosis complicated by a fracture of proximal end of the femur.Materials and methods. In a prospective cohort study, 14 patients received zoledronic acid for 2 years.Results. When comparing BMD L2-L4, it was revealed that a year after the start of treatment, its increase relative to the baseline value was 4.6%, but was statistically insignificant (0.86 ± 0.078 g/cm2 versus 0.90 ± 0.08 g/cm2, p > 0.05). After 2 years of treatment, the BMD of this segment increased, relative to the baseline values, by 12% and the differences became statistically significant (0.86 ± 0.078 g/cm2 compared to 0.97 ± 0.076 g/cm2, p < 0.05). The increase in BMD for the second year of treatment by 6% was statistically significantly different from the increase for the first year of treatment (0.90 ± 0.08 g/cm2 compared to 0.97 ± 0.076 g/cm2, p < 0.05).A comparative analysis of the basic units of the IPC hip after 1 and 2 years of treatment did not reveal significant differences: 0.7075 ± 0.046 g/cm2 compared to 0.7079 ± 0.034 g/cm2 and 0.70751 ± 0.046 g/cm2 compared to 0.6630 ± 0.97 g/cm2, p > 0.05. In any case, for 2 years not marked new vertebral body fractures. Only one patient had a fracture of the radius in the distal third. The quality of life, after 2 years, significantly improved on the scale of “habitual daily activities” (p = 0.007), decreased indicators on the scale of “anxiety” and “depression” (p > 0.05).Discussion. The study confirmed that even in the presence of pronounced bone loss, pharmacological correction of impaired remodeling reduces the risk of new fractures and improves the quality of life.Conclusion. Pharmacotherapy with zoledronic acid, in our study, confirmed its effectiveness in the treatment of osteoporosis.

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