New Frontiers in Osteoporosis Therapy

2020 ◽  
Vol 71 (1) ◽  
pp. 277-288 ◽  
Author(s):  
Cheng Cheng ◽  
Kelly Wentworth ◽  
Dolores M. Shoback
Keyword(s):  
Genetic Disorders ◽  
Femoral Fractures ◽  
Clinical Trial Data ◽  
Osteonecrosis Of The Jaw ◽  
Bone Biology ◽  
Mineral Density ◽  
Osteoporosis Therapy ◽  
Peptide Analog ◽  
Sequential Treatments

Current osteoporosis medications reduce fractures significantly but have rare and serious adverse effects (osteonecrosis of the jaw, atypical femoral fractures) that may limit their safety for long-term use. Insights from basic bone biology and genetic disorders have led to recent advances in therapeutics for osteoporosis. New approaches now in clinical use include the antisclerostin monoclonal antibody romosozumab, as well as the parathyroid hormone–related peptide analog abaloparatide. Clinical trial data show significant antifracture benefits with recently approved romosozumab. Studies using abaloparatide build on our longstanding experience with teriparatide and the importance of consolidating the bone mineral density gains achieved from an anabolic agent by following it with an antiresorptive. Combination and sequential treatments using osteoporosis medications with different mechanisms of action have also been tested with promising results. On the horizon is the potential for cell-based therapies (e.g., mesenchymal stem cells) and drugs that target the elimination of senescent cells in the bone microenvironment.

scholarly journals Duration of Bisphosphonate Drug Holidays in Osteoporosis Patients: A Narrative Review of the Evidence and Considerations for Decision-Making

2021 ◽  
Vol 10 (5) ◽  
pp. 1140
Author(s):  
Kaleen N. Hayes ◽  
Elizabeth M. Winter ◽  
Suzanne M. Cadarette ◽  
Andrea M. Burden
Keyword(s):  
Surrogate Marker ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Narrative Review ◽  
Drug Holiday ◽  
Future Research ◽  
Mineral Density ◽  
First Line Therapy

Bisphosphonates are first-line therapy for osteoporosis, with alendronate, risedronate, and zoledronate as the main treatments used globally. After one year of therapy, bisphosphonates are retained in bone for extended periods with extended anti-fracture effects after discontinuation. Due to this continued fracture protection and the potential for rare adverse events associated with long-term use (atypical femoral fractures and osteonecrosis of the jaw), a drug holiday of two to three years is recommended for most patients after long-term bisphosphonate therapy. The recommendation for a drug holiday up to three years is derived primarily from extensions of pivotal trials with alendronate and zoledronate and select surrogate marker studies. However, certain factors may modify the duration of bisphosphonate effects on a drug holiday and warrant consideration when determining an appropriate time off-therapy. In this narrative review, we recall what is currently known about drug holidays and discuss what we believe to be the primary considerations and areas for future research regarding drug holiday duration: total bisphosphonate exposure, type of bisphosphonate used, bone mineral density and falls risk, and patient sex and body weight.

scholarly journals THERAPY OF ENDOCRINE DISEASE: Denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis

2018 ◽  
Vol 179 (1) ◽  
pp. R31-R45 ◽  
Author(s):  
Athanasios D Anastasilakis ◽  
Stergios A Polyzos ◽  
Polyzois Makras
Keyword(s):  
Fracture Risk ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Mineral Density ◽  
Atypical Femoral Fractures ◽  
Term Administration ◽  
Treatment Naïve ◽  
Fracture Risk Reduction ◽  
Pretreated Patients

The most widely used medications for the treatment of osteoporosis are currently bisphosphonates (BPs) and denosumab (Dmab). Both are antiresorptives, thus targeting the osteoclast and inhibiting bone resorption. Dmab achieves greater suppression of bone turnover and greater increases of bone mineral density (BMD) at all skeletal sites, both in naïve and pretreated patients. No superiority on fracture risk reduction has been documented so far. In long-term administration, BPs reach a plateau in BMD response after 2–3 years, especially at the hip, while BMD increases progressively for as long as Dmab is administered. Both BPs and Dmab are generally considered safe, although they have been correlated to rare adverse events, such as osteonecrosis of the jaw and atypical femoral fractures. Dmab should be preferred in patients with impaired renal function. BPs are embedded in the bone, from which they are slowly released during bone remodeling, therefore continuing to act for years after their discontinuation. In contrast, Dmab discontinuation fully and rapidly reverses its effects on bone markers and BMD and increases the risk for fractures; therefore, Dmab discontinuation should be discouraged, especially in previously treatment-naïve patients, regardless of the conventional fracture risk. In case of discontinuation, other treatment, mainly BPs, should immediately follow, although the optimal sequential treatment strategy is yet to be defined. Combination of teriparatide with Dmab or zoledronic acid, but not alendronate, provides increased BMD gains at all sites. In conclusion, both BPs and Dmab are safe and efficient therapeutic options although their particularities should be carefully considered in an individual basis.

Medication-Induced Musculoskeletal Changes

2019 ◽  
pp. 322-326
Author(s):  
Winnie A. Mar
Keyword(s):  
Musculoskeletal System ◽  
Gold Standard ◽  
Imaging Modality ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Atypical Femoral Fractures ◽  
Osteoblastic Activity ◽  
Induced Changes

Chapter 117 discusses common medication-induced changes of the musculoskeletal system. The effect of corticosteroids on the musculoskeletal system, including osteoporosis and osteonecrosis, is discussed. Corticosteroids decrease osteoblastic activity, stimulate bone resorption, and decrease intestinal absorption of calcium. Complications of bisphosphonate therapy such as atypical femoral fractures and osteonecrosis of the jaw are reviewed. Myopathies and tendon pathologies are briefly discussed, as well as bony changes potentially seen with long-term voriconazole treatment. For osteoporosis, DXA scan is the gold standard, whereas radiography is usually the first imaging modality performed in patients on voriconazole therapy who present with pain.

scholarly journals Osteonecrosis of the Jaw After Osteoporosis Therapy With Denosumab Following Long-term Bisphosphonate Therapy

2013 ◽  
Vol 88 (4) ◽  
pp. 418-419 ◽  
Author(s):  
Tilman D. Rachner ◽  
Uwe Platzbecker ◽  
Dieter Felsenberg ◽  
Lorenz C. Hofbauer
Keyword(s):  
Osteonecrosis Of The Jaw ◽  
Bisphosphonate Therapy ◽  
Osteoporosis Therapy

scholarly journals Do bisphosphonate-related atypical femoral fractures and osteonecrosis of the jaw affect the same group of patients? A pilot study

2014 ◽  
Vol 6 (1) ◽  
Author(s):  
Haitham Afif ◽  
Sebastian Mukka ◽  
Göran Sjödén ◽  
Arkan S. Sayed-Noor
Keyword(s):  
Clinical Practice ◽  
Pilot Study ◽  
Femoral Fractures ◽  
Osteonecrosis Of The Jaw ◽  
Simultaneous Occurrence ◽  
Limited Sample ◽  
Atypical Femoral Fractures ◽  
Limited Sample Size ◽  
Dental Records

Bisphosphonates (BPs) are commonly used drugs in clinical practice. In this pilot study, we investigated whether bisphosphonate-related atypical femoral fractures (AFF) and osteonecrosis of the jaw (ONJ) occurred simultaneously in the same group of patients. Six ONJ patients were examined by an orthopedic surgeon and 5 AFF patients were examined by a dentist to look for manifestations of simultaneous occurrence of AFF in ONJ patients and <em>vice versa</em>. The required radiological investigations and previous medical and dental records were available. No simultaneous occurrence of AFF and ONJ was found in the examined patients. In this pilot study with limited sample size, no manifestations of simultaneous occurrence of AFF and ONJ were found. This could be an indication that these complications have different pathophysiologies and affect different subgroups of patients on long-term BP treatment.

scholarly journals The impact of long-term biologics/target therapy on bone mineral density in rheumatoid arthritis: a propensity score-matched analysis

Rheumatology ◽  
2020 ◽  
Vol 59 (9) ◽  
pp. 2471-2480 ◽  
Author(s):  
Jia-Feng Chen ◽  
Chung-Yuan Hsu ◽  
Shan-Fu Yu ◽  
Chi-Hua Ko ◽  
Wen-Chan Chiu ◽  
...  
Keyword(s):  
Propensity Score ◽  
Propensity Score Matching ◽  
Target Therapy ◽  
Lumbar Vertebra ◽  
Mineral Density ◽  
Osteoporosis Therapy ◽  
Group I ◽  
Group Ii ◽  
The Impact

Abstract Objectives To investigate changes in BMD in RA patients receiving 3-year biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or conventional synthetic DMARD (csDMARD). Methods Patients with RA were recruited from September 2014 until March 2019. Clinical characteristics, BMD and evidence of fragility fractures at enrolment were documented. Participants were treated according to the National Institute for Health and Care Excellence (NICE) guidelines over a 3-year observation period. Repeated BMD was measured at the end of the study period. Participants were grouped into those receiving b/tsDMARD or csDMARD and by propensity score matching (1:2). Results A total of 388 participants completed the 3-year follow-up. After propensity score matching, 92 and 184 participants were allocated to the b/tsDMARD (Group I) and csDMARD (Group II), respectively. After 3 years, BMD remained stable at the femoral neck (FN), hip (total) (TH) and lumbar vertebra (L1-4) (P =0.09, 0.15, 0.87) in Group I. However, BMD decreased significantly in Group II (P=0.045, &lt;0.001, 0.004) at corresponding sites. Participants receiving combined b/tsDMARD and anti-osteoporosis therapy experienced a greater BMD preserving effect than other subgroups. Conclusion Long-term b/tsDMARDs therapy had protective effects on bone loss for patients with RA. Patients receiving concomitant anti-osteoporosis therapy and b/tsDMARDs therapy experienced the greatest BMD preserving effect.

scholarly journals AB0617 BISPHOSPHONATES DANS L’OSTÉOPOROSE ET LE RISQUE D’OSTÉONÉCROSE DE LA MÂCHOIRE, ENVIRON 896 CAS

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1343.1-1343
Author(s):  
A. R. Halidou ◽  
K. Nassar ◽  
S. Janani
Keyword(s):  
Lumbar Spine ◽  
Femoral Neck ◽  
Corticosteroid Therapy ◽  
Osteonecrosis Of The Jaw ◽  
Mineral Density ◽  
Duration Of Treatment ◽  
Treatment Of Osteoporosis ◽  
Total Hip ◽  
T Score

Background:Bisphosphonates (BF) are used in the treatment of osteoporosis, Paget’s disease of bone, hypercalcemia and in patients with cancer. When used to treat osteoporosis, the optimal duration of treatment is 3 to 5 years; however, their long-term use has been rarely associated with osteonecrosis of the jaw.Objectives:To assess the risk of developing osteonecrosis of the jaw in patients followed for osteoporosis and on bisphosphonates (BP).Methods:Type of study: retrospective study conducted at the rheumatology department of the IBN ROCHD CHU in Casablanca.Duration: from October 2013 to October 2020 (7 years).Inclusion criteria: all patients followed for osteoporosis in the weakening osteopathies unit of the bone and treated with oral or intravenous bisphosphonates.Exclusion criteria: patients followed for other than osteoporosis.Results:896 patients were treated during this period. The average age was 62.74 years (28 to 90 years), of which 85.16% were women and 14.84% were men, for a sex ratio (F / M) of 5.74. As a history, 18.75% of patients are diabetic, 26.56% followed for breast neoplasm, 14.06% of patients had received long-term corticosteroid therapy for various pathologies such as chronic inflammatory rheumatism. Osteoporosis was postmenopausal in 687 patients, ie 76.67% of cases, 14.06% after long-term corticosteroid therapy, 8.15% following hormone therapy (anti-aromatases) and 6.92% following chemotherapy; note that 18.16% of these patients were found in at least two of the situations. The mean bone mineral density (BMD), T-score pair considered in all [T-score (BMD)] is -3 (0.736) in the lumbar spine (L1-L4), -2.9 (0.658) at the femoral neck, -2.6 (0.804) at the total hip before the start of treatment. 69.97% of the patients were put on Alendronic acid, 12.50% on Residronic acid, 10.93% on Zolidronic acid, 3.46% on Pamidronic acid and 3.14% received Strontium Ranelate, note that before the start of the treatment all the patients benefited from a dental consultation followed by care of any lesions, the bisphosphonates were only introduced after having ruled out all their dental contraindications, the average duration of treatment for all the molecules was 4.71 years (2 to 5 years) and no patient developed osteonecrosis of the jaw. The change in control BMD on average after 2 years of treatment was -2.7 (0.782) at the lumbar spine, -2.6 (0.749) at the femoral neck and -2.4 (0.713) at the hip total, after 5 years -2.4 (0.874) at the spine, -2.1 (0.809) at the femoral neck and -1.93 (861) at the total hip.Conclusion:The occurrence of ONJ in the treatment of osteoporosis with the use of BFs is rare, and appears to be unpredictable; but maintaining therapeutic caution, consisting in diagnosing and treating any dental lesions before starting treatment, can considerably reduce or even cancel the risk of occurrence; especially in patients treated with long-term intravenous pamidronate.References:[1]Dr Halidou Idrissa Abdoul-Rahamane, Pr Kawtar Nassar, PR Saadia Janani.[2]Rheumatology department of the IBN ROCHD CHU in CASABLANCA. Casablanca Faculty of Medicine and Pharmacy. Hassan II University. MoroccoDisclosure of Interests:None declared.

scholarly journals NIH PATHWAYS TO PREVENTION WORKSHOP: RESEARCH GAPS FOR LONG-TERM DRUG THERAPIES FOR FRACTURE PREVENTION

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S748-S748
Author(s):  
Lyndon Joseph ◽  
Faye Chen
Keyword(s):  
Medical Condition ◽  
Scientific Evidence ◽  
Femoral Fractures ◽  
Osteoporotic Fractures ◽  
Fracture Prevention ◽  
Osteonecrosis Of The Jaw ◽  
Drug Discontinuation ◽  
Serious Adverse Events ◽  
The Impact

Abstract The NIH Pathways to Prevention Workshop was held on October 30-31, 2018 to present scientific evidence, as well as physician and patient perspectives to better understand the benefits and harms of drug therapies for osteoporosis fracture prevention. Osteoporotic fractures lead to substantial morbidity, mortality, and economic costs. The underlying medical condition, is a skeletal disorder characterized by compromised bone strength predisposing to increased fracture risk. Several medications approved by the U.S. Food and Drug Administration to prevent osteoporotic fractures have been effective when taken by people who are at high risk of fracture. These include bisphosphonates , denosumab, teriparatide, estrogens, and selective estrogen-receptor modulators. However, rare but serious adverse events, such as atypical femoral fractures and osteonecrosis of the jaw associated with bisphosphonates have raised questions regarding the safety of their use. There is limited evidence on the benefits and harms of long-term osteoporosis drug therapy, including the timing and duration of drug discontinuation or drug holidays. It is not clearly known which patients will benefit or may be harmed from continued drug intervention, who should and should not be put on drug holiday, how to identify such patients and properly treat them, and how to predict their outcomes. Key scientific areas covered by the workshop included: the benefits and risks of osteoporotic drugs with short-term and long-term use and factors that influence outcomes; the impact of drug discontinuation and drug holidays on outcomes; and patient and clinician factors that impact the use of and adherence to osteoporotic drugs.

scholarly journals The problem of low adherence to antiresorptive therapy with bisphosphonates: solutions

2022 ◽  
pp. 175-180
Author(s):  
O. V. Yakushevskaya
Keyword(s):  
Cost Effective ◽  
Rehabilitation Program ◽  
Antiresorptive Therapy ◽  
Mineral Density ◽  
Osteoporosis Therapy ◽  
Treatment Of Osteoporosis ◽  
Demographic Situation ◽  
Natural Result

Over the past several decades, there has been a global aging of the population around the world. The demographic situation in the Russian Federation is no exception, being a natural result of an increase in the life expectancy of the population. In clinical practice, geriatric diseases have been identified and are widely studied, which deserve priority attention due to a sharp decline in the quality of life of elderly patients. Osteoporosis is called a “silent epidemic” among elderly and senile patients. This disease is associated with a high risk of low-traumatic fractures of various localization. The imperfect rehabilitation program after complex fractures and its insufficient funding are forcing clinicians to focus on more cost-effective solutions to this problem  – the  prevention and treatment of  osteoporosis. Osteomodifying agents are widely used by physicians of  various specialties. Bisphosphonates effectively reduce the risk of low-traumatic fractures against the background of an increase in bone mineral density. The  level of  effectiveness of  bisphosphonates depends on the  patient’s adherence to antiresorptive therapy and the degree of compensation for vitamin D and serum calcium. Low adherence to osteoporosis therapy is based on the need for long-term use of bisphosphonates and a different spectrum of adverse events. In the article, using alendronate as an example, the problem of low adherence to antiresorptive therapy will be considered and ways to solve it are presented.

scholarly journals Bilateral Atypical Femoral Fracture(AFF) After Teriparatide and Subsequent Anti-Resorptive Therapy: A Management Dilemma

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A184-A184
Author(s):  
Chandrika Reddy ◽  
Mohsen Zena ◽  
John C Gallagher ◽  
Robert R Recker ◽  
Robert J Anderson
Keyword(s):  
Femoral Fractures ◽  
Surgical Care ◽  
Mineral Density ◽  
Atypical Femoral Fractures ◽  
Dxa Scan ◽  
Increased Sensitivity ◽  
Healing Bone ◽  
Sclerostin Antibody ◽  
Dental Work

Abstract Introduction: Femoral fractures carry devastating morbidity for long term ambulation. Atypical femoral fractures (AFF) are uncommon, and bilateral AFFs are more rare with added post-fracture limitations. We report two patients with bilateral AFFs despite receiving teriparatide (TPTD). Case 1: A 72 y.o. Filipino lady with osteoporosis since late 1990 was treated with bisphosphonates (BP) intermittently over 25 years with drug holidays for dental work. She stopped alendronate in mid-2013 and continued raloxifene. She suffered a spontaneous left mid-femur AFF in June, 2015 that was treated with intramedullary (IM) rod and nailing. In July, 2015 she started TPTD 20 mcg daily for 23 months until May, 2017. Alendronate was restarted weekly. In December, 2018 she developed right thigh and hip prodromal pain without x-ray changes. In April, 2019 (46 months after the left AFF and 23 months after TPTD), she sustained a spontaneous right sub-trochanteric AFF. BP was stopped. After IM rod and nailing, she began a second course of TPTD. Case 2: 72 y.o Caucasian lady with osteoporosis since 2000 was treated with alendronate until April, 2006. She was switched to daily TPTD for 22 months from May, 2006 to March, 2008. Oral BP was resumed in April, 2008. She suffered a left AFF in November, 2009; BP was stopped in March, 2010. In July, 2010 she sustained a right AFF (9 months after the left AFF and 28 months post-TPTD). Each spontaneous AFF occurred after prodromal pain, and each was treated with IM rod placement with nailing. She received BP infusion in 2011 and TPTD from March, 2012 to March, 2014. DXA scan in 2020 showed lumbar spine osteopenia. She currently takes calcium and Vit D supplementation. Discussion: TPTD is reported as a potential treatment for enhancing AFF healing, bone mineral density and pain resolution. The expectation is that it might prevent contralateral AFF. No randomized studies of prevention of AFF with TPTD exist. Available reports show variable results. Prolonged presence of BP in bone may contribute to this variation. We identified 7 reported AFF patients treated with TPTD who then developed a contralateral AFF. We found 2 patients with new AFF after TPTD as in our Case 2. In all cases there was previous exposure to BP. Perhaps the 28–30% risk of a contralateral AFF within 4 years in the setting of BP is irremediable. Conclusion: TPTD increases healing of AFF in some reports, but prevention of an initial or further AFF has not been well documented. Our 2 patients and 9 others reported suggest a possible subset with increased sensitivity to the effect of BP and increased AFF risk. The best choice after TPTD is unclear, but it may include permanent removal of anti-resorptive agents. The anti-sclerostin antibody romosozumab also has been associated with AFF. Choices are limited for these patients other than excellent surgical care, adequate calcium/vitamin D intake, and periodic imaging as symptoms dictate.

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