Therapy For Treatment Of Osteoporosis Research Articles

The interplay of rheumatoid arthritis and osteoporosis: exploring the pathogenesis and pharmacological approaches.

Rheumatoid arthritis (RA) and osteoporosis are two chronic disorders that are often seen together. RA is an autoimmune disorder that causes pain and inflammation in the joints, while osteoporosis is a disorder in which the bones become weak and fragile. Risk factors for bone loss in RA include disease activity, longer disease duration, erosive disease, autoantibody positivity, and joint damage leading to impaired physical activity. Recent research has shown that there is a complex interplay between immune cells, cytokines, and bone remodeling processes in both RA and osteoporosis. The bone remodeling process is regulated by cytokines and immune system signaling pathways, with osteoclasts activated through the RANK/RANKL/OPG pathway and the Wnt/DKK1/sclerostin pathway. Understanding these mechanisms can aid in developing targeted therapies for treatment of osteoporosis in RA patients. Current pharmacological approaches include anti-osteoporotic drugs such as bisphosphonates, denosumab, teriparatide, abaloparatide, raloxifene, and romosozumab. Conventional disease-modifying antirheumatic drugs such as methotrexate and biologicals including TNF inhibitors, IL-6 inhibitors, rituximab, and abatacept lower disease activity in RA and can improve bone metabolism by reducing inflammation but have limited impact on bone mineral density. This review will shed light on the relationship between osteoporosis and rheumatoid arthritis as well as the various factors that influence the onset of osteoporosis in RA patients. We also explore several treatment approaches to effectively managing osteoporosis in RA patients.

THU450 Looking Beyond The Usual Suspects: A Rare Case Of Teriparatide Induced Gynecomastia

Abstract Disclosure: B.P. Ramchandani: None. F.S. Mirza: None. Introduction: Teriparatide (TP) is a parathyroid hormone analogue used as anabolic therapy for treatment of osteoporosis. Common side effects include nausea, headache and orthostatic hypotension. We hereby describe the first case of gynecomastia that developed shortly after starting treatment with TP, and resolved a couple of months after discontinuation of therapy. Clinical Case: A 61 year old male physician with severe osteoporosis presented to the endocrinology clinic with bilateral nipple tenderness and a firm lump under the left areolar region four months after starting therapy with TP. There was no associated bleeding or nipple discharge. He denied having any erectile dysfunction or decline in sexual function. His medications included vitamin D, lansoprazole and rosuvastatin. Family history was significant for osteoporosis and ductal carcinoma in situ in mother, and bilateral hip fractures after falls in his father at the age of 80. He denied any alcohol or recreational drug use. He was physically active but denied any recent weight loss. Other than the firm glandular tissue under left lateral areola, no other findings including nipple inversion or lymphadenopathy were noted on exam. Laboratory testing showed normal total and free testosterone level at 360 ng/dl and 68 pg/ml respectively, estradiol 39 pg/ml, LH 1.44 mIU/ml, FSH 4.44 mIU/ml, TSH 1.71 uIU/L, Prolactin 4.54 ng/ml and HCG <2 IU/ml, along with normal creatinine and liver enzymes. Mammogram showed left greater than right flame-shaped focal asymmetry contiguous with the nipple compatible with gynecomastia. Breast ultrasound showed left greater than right retroareolar dendritic slightly hypoechoic soft tissue correlating with the mammographic findings. Due to significant discomfort associated with gynecomastia, a decision was made to stop TP and treatment with risedronate was initiated. Following the discontinuation of the drug, the patient reported that his symptoms gradually improved and the nipple sensitivity and the palpable swelling of the left breast completely resolved at his follow up visit four months later. Conclusion: The temporal association between the initiation of teriparatide treatment and onset of gynecomastia, and improvement of the symptoms and physical findings upon discontinuation of the drug suggests that teriparatide was the likely cause of gynecomastia in our patient. Presentation: Thursday, June 15, 2023

Testosterone Replacement Therapy for Treatment of Osteoporosis in Men

Testosterone Replacement Therapy for Treatment of Osteoporosis in Men

The Role of Non-Pharmacological Treatment for Osteoporosis at Patients with High Plasmatic Concentration of ACTH

Cushing disease is characterized by the hypersecretion of adrenocorticotropic hormone (ACTH) due to a pituitary adenoma that causes endogenous hypercortisolism by stimulating adrenal glands. Objective of the study was to analyse the benefits of the physical therapy for patients with ACTH-secreting adenomas osteoporosis.This retrospective study was performed at Craiova, Bunavestire Hospital, the patients were monitorized during 6 months and included 17 patients with ACTH-secretingadenomas. Participants in this study group exercised 3 days a week for 6 consecutive months. Each session is intended to take approximately 60 minutes to complete and will comprise of a warm-up, progressive resistance training using medium weights, moderate impact weight-bearing exercises, flexibility and also stretching exercises. Physical therapy for osteoporosis treatment in patients with ACTH-secreting adenomas improved joint mobility and reduced pain, significantly increasing BMD performed by DEXA in group I patients compared to patients included in group II. Pain relief is evident following evaluation using the VAS rating scale. The increase in joint mobility is observed following the goniometric measurement from day 1 to the end of treatment. Applying the physical therapy program the bone pain and joint mobility was improved, physical therapy can modify bone turnover in the sense of increasing the body mass.

A case of atypical femur fracture during long-term treatment with bisphosphonates in patient with postmenopausal osteoporosis

Bisphosphonates is a first-line therapy for treatment of osteoporosis. In the last decade, the number of atypical femur fracture (AFF) cases during long-term treatment with bisphosphonates has increased. The aim of this article was to analyze the literature data on this problem, to define the diagnostic criteria of AFF and to present the case of AFF in the patient who received treatment with alendronate for 3.5 years.
 A 78-year-old woman, receiving oral bisphosphonate for severe postmenopausal osteoporosis for 3.5 years, suddenly started feeling pain in her right thigh while walking. Three months later, she had got a fracture in middle third of the right femur after falling from her standing height. According to instrumental diagnostics, this fracture had all criteria of AFF. Blocking intramedullary osteosynthesis with shafts was performed. A retrospective analysis of soft tissue magnetic resonance imaging in the area of right thigh, done before the fracture, showed the presence of undiagnosed incomplete right femur fracture in the middle third, which subsequently led to a complete fracture.
 Presented clinical case demonstrates the complexity of AFF diagnostics. The purpose of the publication is to draw attention of medical specialists to the issue of this rare side effect of bisphosphonate treatment.

Prevention and management of osteoporosis and osteoporotic fractures in persons with a spinal cord injury or disorder: A systematic scoping review

Objectives: The primary objective was to review the literature regarding methodologies to assess fracture risk, to prevent and treat osteoporosis and to manage osteoporotic fractures in SCI/D.Study Design: Scoping review.Settings/Participants: Human adult subjects with a SCI/D.Outcome measures: Strategies to identify persons with SCI/D at risk for osteoporotic fractures, nonpharmacological and pharmacological therapies for osteoporosis and management of appendicular fractures.Results: 226 articles were included in the scoping review. Risk of osteoporotic fractures in SCI is predicted by a combination of DXA-defined low BMD plus clinical and demographic characteristics. Screening for secondary causes of osteoporosis, in particular hyperparathyroidism, hyperthyroidism, vitamin D insufficiency and hypogonadism, should be considered. Current antiresorptive therapies for treatment of osteoporosis have limited efficacy. Use of surgery to treat fractures has increased and outcomes are good and comparable to conservative treatment in most cases. A common adverse event following fracture was delayed healing.Conclusions: Most of the research in this area is limited by small sample sizes, weak study designs, and significant variation in populations studied. Future research needs to address cohort definition and study design issues.

Is there a role for combination therapy for osteoporosis?

There is no single agent currently available that represents a cure for osteoporosis. Various anabolic and antiresorptive therapies have been combined, following different protocols, to attempt to attain superior bone mass and strength compared to monotherapy. There is a great deal of misunderstanding about results of these trials. The small randomized, blinded study in men with osteoporosis in this issue of the journal [1], evaluating a previously untested combination of teriparatide and risedronate compared with either agent alone, might help encourage some reconsideration of combination therapy for treatment of osteoporosis. In trying to interpret the many different combination therapy studies [2, 3], it is important to make some distinctions between the populations that have been studied: previously untreated individuals receiving two agents concomitantly and individuals on established antiresorptive therapy where the anabolic agent is combined with continued antiresorptive therapy. While there are some parallels between these two populations, differences in the magnitude of active bone surface, effects of acute antiresorptive agents on parathyroid dynamics, and perhaps unique acute effects of antiresorptive agents on osteoblast function might all play a role in producing distinct responses to combination therapy in previously treated vs treatment naive individuals. A third population of individuals who have been on prior bisphosphonates in the recent or remote past has not been adequately studied. Several lines of work suggested that in patients who had already been treated with an oral bisphosphonate such as alendronate, there might be different effects in those who switched to teriparatide [4–6] vs those in whom teriparatide was added [7]. In general, hip BMD declines in the first 6–12 months when teriparatide is given alone to these pretreated patients, whereas bone density increases modestly in those on combination treatment. In the only study to directly compare the effects of switching to teriparatide vs combining teriparatide with ongoing alendronate (in women who had already received prior alendronate for an average of over 4 years), DXA BMD changes in both spine and hip were greater in those randomized to combination therapy than teriparatide alone [8]. Furthermore, volumetric BMD of the hip declined in those who switched to teriparatide and increased in those who received combination therapy [9]. Although strength of the hip did not actually decline in the teriparatide alone group, hip strength increased in the combination group [9]. These findings have very important implications for the clinical use of teriparatide in patients who have received prior antiresorptive therapy and are at high risk for hip and other skeletal sites that are rich in cortical bone. It may be that the withdrawal of the bisphosphonate actually facilitates an exaggerated bone resorption response to teriparatide [8] and offsets the expected positive bone balance, particularly in the cortical skeleton where there is little incorporated bisphosphonate. Some of the findings in this pretreated population can be applied to those of combination therapy studies in the treatment naive population. In several of these studies, there was no apparent difference at 12 months in the response of spine BMD measured by DXA to combination treatment versus PTH or teriparatide monotherapy [10, 11], whereas a greater increase in hip BMD was seen with combination treatment compared to teriparatide alone. Even a short-term study of teriparatide plus raloxifene was consistent with these findings [12]; there was no difference F. Cosman (&) Helen Hayes Hospital, West Haverstraw, NY, USA e-mail: cosmanf@helenhayeshosp.org

5 mg zoledronic acid for treatment of postmenopausal women with osteoporosis and osteoporotic fracture

Objective To investigate the effect of once yearly zoledronic acid of 5 mg on postmenopausal women with osteoporosis of different causes. Methods From October 2009 to December 2009,a total of 89 postmenopausal women with osteoporosis were enrolled and assigned into 2 groups.There were 45 cases of primary postmenopausal osteoporosis,including 27 cases of fresh fracture,in group A.They were aged from 47 to 83 years,with an average of 63.7 years.There were 44 cases of secondary postmenopausal osteoporosis,including 28 cases of fresh fracture,in group B.All patients were given a.single 30-minute intravenous injection of zoledronic acid (5 mg),supplemented by 1,25-dihydroxyvitamin D of 0.25 μg and calcium of 600 mg with VitD125 IU daily.At pre-intervention and 12 months after intervention respectively,bone mineral density (BMD) was measured by dual-X-ray absorptiometry (DXA) at the lumbar spine and hip,and a balance test(Sunlight Tetrax- Ⅱ) was performed to evaluate the risk of falling.Intervention compliance of the patients and adverse events related to zoledronic acid infusion were observed. Results All cases of fresh fracture healed well at 3-month follow-up.At 12 months,43 subjects in group A and 42 subjects in group B completed the follow-up.In group A,BMD increased by 5.8％ at the lumbar spine,by 2.9％ at the femoral neck,by 5.2％ at the Words area,by 5.3％ at the greater trochanter and by 3.9％ at the total hip while the risk of falling decreased by 26.1％; in group B,BMD increased by by 3.4％ at the lumbar spine,by 2.1％ at the femoral neck,by 3.2％ at the Words area,by 3.0％ at the greater trochanter and by 2.5％ at the total hip while the risk of falling decreased by 21.8％.The differences between pre-intervention and post-intervention were significant in both groups ( P ＜ 0.05).No intolerable adverse events occurred in both groups except that one new fracture happened in each group but responded to conservative treatment.Conclusion A once-yearly infusion of zoledronic acid of 5 mg is a convenient and effective therapy for treatment of osteoporosis in postmenopausal women. Key words: Pharmacotherapy; Osteoporosis, postmenopausal; Fractures; Bone density; Risk of falling

MicroRNA-138 regulates osteogenic differentiation of human stromal (mesenchymal) stem cells in vivo

Elucidating the molecular mechanisms that regulate human stromal (mesenchymal) stem cell (hMSC) differentiation into osteogenic lineage is important for the development of anabolic therapies for treatment of osteoporosis. MicroRNAs (miRNAs) are short, noncoding RNAs that act as key regulators of diverse biological processes by mediating translational repression or mRNA degradation of their target genes. Here, we show that miRNA-138 (miR-138) modulates osteogenic differentiation of hMSCs. miRNA array profiling and further validation by quantitative RT-PCR (qRT-PCR) revealed that miR-138 was down-regulated during osteoblast differentiation of hMSCs. Overexpression of miR-138 inhibited osteoblast differentiation of hMSCs in vitro, whereas inhibition of miR-138 function by antimiR-138 promoted expression of osteoblast-specific genes, alkaline phosphatase (ALP) activity, and matrix mineralization. Furthermore, overexpression of miR-138 reduced ectopic bone formation in vivo by 85%, and conversely, in vivo bone formation was enhanced by 60% when miR-138 was antagonized. Target prediction analysis and experimental validation by luciferase 3' UTR reporter assay confirmed focal adhesion kinase, a kinase playing a central role in promoting osteoblast differentiation, as a bona fide target of miR-138. We show that miR-138 attenuates bone formation in vivo, at least in part by inhibiting the focal adhesion kinase signaling pathway. Our findings suggest that pharmacological inhibition of miR-138 by antimiR-138 could represent a therapeutic strategy for enhancing bone formation in vivo.

Zoledronic acid infusion for prevention and treatment of osteoporosis

Osteoporotic fractures are associated with significant morbidity, reduced quality of life, increased mortality, and high health care costs. Bisphosphonates are standard therapy for treatment of osteoporosis. However, patient compliance and persistence with oral weekly or monthly bisphosphonate therapy are suboptimal and may lead to reduced effectiveness. Zoledronic acid (ZOL) is an intravenous bisphosphonate that is given once yearly for the treatment of osteoporosis via a medically supervised 15-minute infusion. This ensures compliance for a full 12 months. In clinical trials, an annual infusion of ZOL 5 mg has shown sustained efficacy in reducing hip and spine fractures in postmenopausal women with osteoporosis. It has also been shown to increase bone density in postmenopausal women with osteopenia (low bone mass) and in men with osteoporosis. Transient flu-like symptoms are the most common adverse effects following ZOL infusion, and these can generally be managed with acetaminophen. The availability of an intravenous bisphosphonate that ensures compliance over a long dosing interval may help to overcome barriers to efficacy resulting from poor long-term compliance with oral agents.

Underuse of Procedures for Diagnosing Osteoporosis and of Therapies for Osteoporosis in Older Nursing Home Residents

Objective To investigate the prevalence of osteoporosis, the prevalence of utilization of bone mineral density (BMD) measurements for diagnosis of osteoporosis, and prevalence of use of calcium and vitamin D supplements and other antiresorptive therapies for treatment of osteoporosis in postmenopausal women in an academic nursing home. Methods The charts of all women aged 56 years and older residing in an academic nursing home were analyzed by one of the authors for the prevalence of osteoporosis, the prevalence of use of BMD measurements to diagnose osteoporosis, and the prevalence of use of calcium and vitamin D supplements and other antiresorptive therapies for treatment of osteoporosis. Results Of 136 postmenopausal women, mean age 79 ± 10 years, 66 (49%) had measurements of BMD. Of these 66 women, 31 (47%) had osteoporosis, 21 (32%) had osteopenia, and 14 (21%) had normal BMD. Elemental calcium carbonate 1500 mg daily was prescribed to 17 of 31 women (55%) with osteoporosis, to 12 of 21 women (57%) with osteopenia, to 2 of 14 women (14%) with normal BMD, and to 27 of 70 women (39%) with no BMD obtained. Any dose of calcium was prescribed to 78 of 136 elderly women (58%). Vitamin D supplements were prescribed to 13 of 31 women (42%) with osteoporosis, to 9 of 21 women (43%) with osteopenia, to 2 of 14 women (14%) with normal BMD, and to 20 of 70 women (29%) with no BMD obtained. Vitamin D supplements were prescribed to 44 of 136 elderly women (32%). Biphosphonates were prescribed to 19 of 31 women (61%) with osteoporosis. Of 20 women on medications that increased the risk of osteoporosis, 6 (30%) had BMD measured. Nine of these 20 women (45%) were on calcium supplements. Conclusions Older postmenopausal women in an academic nursing home have a high prevalence of osteoporosis and osteopenia, a low prevalence of measurement of BMD, and underuse of calcium, vitamin D supplements, and other antiresorptive therapies for treatment of osteoporosis.

Underuse of procedures for diagnosing osteoporosis and of therapies for osteoporosis in older nursing home residents.

To investigate the prevalence of osteoporosis, the prevalence of utilization of bone mineral density (BMD) measurements for diagnosis of osteoporosis, and prevalence of use of calcium and vitamin D supplements and other antiresorptive therapies for treatment of osteoporosis in postmenopausal women in an academic nursing home. The charts of all women aged 56 years and older residing in an academic nursing home were analyzed by one of the authors for the prevalence of osteoporosis, the prevalence of use of BMD measurements to diagnose osteoporosis, and the prevalence of use of calcium and vitamin D supplements and other antiresorptive therapies for treatment of osteoporosis. Of 136 postmenopausal women, mean age 79 +/- 10 years, 66 (49%) had measurements of BMD. Of these 66 women, 31 (47%) had osteoporosis, 21 (32%) had osteopenia, and 14 (21%) had normal BMD. Elemental calcium carbonate 1500 mg daily was prescribed to 17 of 31 women (55%) with osteoporosis, to 12 of 21 women (57%) with osteopenia, to 2 of 14 women (14%) with normal BMD, and to 27 of 70 women (39%) with no BMD obtained. Any dose of calcium was prescribed to 78 of 136 elderly women (58%). Vitamin D supplements were prescribed to 13 of 31 women (42%) with osteoporosis, to 9 of 21 women (43%) with osteopenia, to 2 of 14 women (14%) with normal BMD, and to 20 of 70 women (29%) with no BMD obtained. Vitamin D supplements were prescribed to 44 of 136 elderly women (32%). Biphosphonates were prescribed to 19 of 31 women (61%) with osteoporosis. Of 20 women on medications that increased the risk of osteoporosis, 6 (30%) had BMD measured. Nine of these 20 women (45%) were on calcium supplements. Older postmenopausal women in an academic nursing home have a high prevalence of osteoporosis and osteopenia, a low prevalence of measurement of BMD, and underuse of calcium, vitamin D supplements, and other antiresorptive therapies for treatment of osteoporosis.

Combination therapy for postmenopausal osteoporosis.

A number of agents have been shown to reduce the risk of fractures in patients with postmenopausal osteoporosis. However, the additional benefits of combination therapy as opposed to monotherapy are uncertain. We performed a MEDLINE search and reviewed the published randomized trials of agents used in combination. Combination therapy results in greater gains in bone mineral density than monotherapy and possibly greater effects on bone turnover. However, none of these studies are large enough or of sufficient duration to determine whether a greater reduction in fracture is achieved. Combination therapy has important cost implications and is likely to be associated with an increased prevalence of adverse events, reduced tolerability and a reduction in adherence. Furthermore, over-suppression of bone turnover as a result of combination antiresorptive therapy might have adverse effects on bone strength, particularly with long-term treatment. Thus, the use of combination therapy for treatment of osteoporosis cannot be recommended on the basis of currently available evidence.