Teriparatide: Its Use in the Treatment of Osteoporosis

2011 ◽  
Vol 3 ◽  
pp. CMT.S2358 ◽  
Author(s):  
Charles A. Inderjeeth ◽  
Kien Chan ◽  
Paul Glendenning
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Animal Studies ◽  
Safety Data ◽  
Ageing Population ◽  
Mineral Density ◽  
Duration Of Treatment ◽  
Treatment Of Osteoporosis ◽  
Teriparatide Treatment ◽  
Increased Risk

The prevalence of osteoporosis is likely to rise with the increase in life expectancy of an ageing population. Current first line therapies for the treatment of osteoporosis are predominantly anti-resorptive. Teriparatide is a first in class, anabolic agent with a unique mechanism that results in increased bone formation. Daily subcutaneous injection for 6–24 months was effective in reducing vertebral and non-vertebral fracture rates, in improving bone mineral density (BMD) and in increasing bone formation rates in postmenopausal osteoporosis, with effects persisting following treatment cessation. Similar benefits on bone mass and bone formation were seen in men with osteoporosis and glucocorticoid induced osteoporosis. Beneficial effects on bone mass have been demonstrated in treatment naive subjects treated with teriparatide alone, sequentially with anti-resorptive therapy and concomitantly with some, but not all, anti-resorptive treatments due to an early blunting of the anabolic effect. Teriparatide is generally well tolerated. However, the high treatment cost and inconvenient mode of administration has limited it's use to patients with osteoporosis who have experienced an unsatisfactory response, who are intolerant to other osteoporosis therapies, or to patients at very high risk of fracture. Teriparatide treatment is currently restricted to a total lifetime treatment dose of 18 months of daily subcutaneous therapy due to concerns from animal studies suggesting an increased risk of osteosarcoma. More safety data may permit a longer duration of treatment in the future but will necessitate prolonged human studies. Teriparatide may serve a more prominent role in the treatment of older patients who continue to fracture despite low bone turnover or sustain side effects with anti-resorptive therapy.

scholarly journals AB0081 THE ROLE OF LOCAL BISPHOSPHONATES IN THE PRESERVATION OF THE BMD IN THE ZONE OF SURGICAL BONE DEFECT (ANIMAL STUDIES)

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1340.1-1341
Author(s):  
A. Torgashin ◽  
S. Rodionova ◽  
A. Torgashina
Keyword(s):  
Bone Formation ◽  
Bone Mass ◽  
Animal Studies ◽  
Control Group ◽  
Mineral Density ◽  
Control Groups ◽  
Physiological Level ◽  
Bone Implant ◽  
Biocomposite Material ◽  
Intervention Zone

Background:One of the reasons for failures in Arthroplasty is the preservation in the postoperative period in the bone adjacent to the implant of the prevalence of resorption over bone formation. The possibility of inhibition of resorption by bisphosphonates, including their local use in the composition of the biocomposite material, aggravates the situation due to the simultaneous oppression of bone formation. A low level of remodeling in these cases leads to a further loss of bone mass in the intervention zone.Objectives:To evaluate in the experiment the effect of bisphosphonates in the biocomposite material on the bone mass both in the surgical intervention zone and in the segment as a whole.Methods:The study was conducted as a comparison with the control. 60 females of white non-linear rats, body weight 130-150 g. were divided into 6 groups. In 3 groups, the defect of the tibia was filled with a biocomposite material in the form of a gel (patent No. 2325170) connected to various bisphosphonates Ibandronic acid (Bonviva), zoledronic acid (Aklasta), alendronate sodium (Fosamax) was used in conjunction with a non-demineralized lyophilized bone implant. Groups, the defect was filled with a non-demineralized lyophilized bone implant with biocomposite material without bisphosphonate, in the second control group, non-demineralized lyophils th e bone implants without biocomposite matreiala in tretey- defect is not filled.Assessment of bone mineral density (BMD) in the intervention area and in the segment as a whole was performed using X-ray densitometry (Hologic, Small Animals Program Performing and Analyzing Small Animal Studies). Results Comparison (simple dispersion analysis) of the MIC of all groups using bisphosphonates on the one hand, with the MIC of all control groups on the other hand, revealed significant differences (p <0.002).Results:The analysis, using the paired t-test, the average MIC values in the combined group using bisphosphonates and the pooled control group, confirmed that the BMD in the zone of intervention in the bisphosphonate group was significantly higher than in the control: 0.320 ± 0.008 g / cm2, respectively, versus 0.285 ± 0.019 g / cm2 (p = 0.002). If the group was excluded from the analysis, where the defect was not filled, the tendency to differences remained: 0.320 ± 0.008 g / cm2 vs. 0.308 ± 0.002 g / cm2 (p = 0.11).Mean BMDs of the whole segment with the use of bisphosphonates also proved to be significantly higher than in the control, both with the inclusion in the analysis of the group without replacement of the defect, and with its exception. Thus, when all control groups were included in the analysis, the mean MIC values in the group with bisphosphonates were 0.30 ± 0.01 g / cm2 vs. 0.272 ± 0.12 g / cm2 (p <0.001). When excluding from the analysis of the group without replacement of the defect, the MIC values were respectively: 0.307 ± 0.01 g / cm2 versus 0.285 ± 0.01 g / cm2 (p = 0.01).Conclusion:Relative to the control, an increase in BMD in the group using bisphosphonates excludes the possibility of their negative impact on the process of bone formation. The marked positive bone balance confirms the ability of bisphosphonates to maintain the remodeling mechanism at the physiological level.References:Local application of bisphosphonates, osteoplastic materials, biocomposite material, bone implant reconstruction, bone formation.Disclosure of Interests:None declared

scholarly journals Osteoarthritis: Insights Offered by the Study of Bone Mass Genetics

2021 ◽  
Vol 19 (2) ◽  
pp. 115-122
Author(s):  
A. Hartley ◽  
C. L. Gregson ◽  
L. Paternoster ◽  
J. H. Tobias
Keyword(s):  
Bone Mass ◽  
Causal Effect ◽  
Mendelian Randomisation ◽  
Mineral Density ◽  
High Bone Mass ◽  
Increased Risk ◽  
High Bone ◽  
Genetic Mechanisms ◽  
Additional Support

Abstract Purpose of Review This paper reviews how bone genetics has contributed to our understanding of the pathogenesis of osteoarthritis. As well as identifying specific genetic mechanisms involved in osteoporosis which also contribute to osteoarthritis, we review whether bone mineral density (BMD) plays a causal role in OA development. Recent Findings We examined whether those genetically predisposed to elevated BMD are at increased risk of developing OA, using our high bone mass (HBM) cohort. HBM individuals were found to have a greater prevalence of OA compared with family controls and greater development of radiographic features of OA over 8 years, with predominantly osteophytic OA. Initial Mendelian randomisation analysis provided additional support for a causal effect of increased BMD on increased OA risk. In contrast, more recent investigation estimates this relationship to be bi-directional. However, both these findings could be explained instead by shared biological pathways. Summary Pathways which contribute to BMD appear to play an important role in OA development, likely reflecting shared common mechanisms as opposed to a causal effect of raised BMD on OA. Studies in HBM individuals suggest this reflects an important role of mechanisms involved in bone formation in OA development; however further work is required to establish whether the same applies to more common forms of OA within the general population.

scholarly journals Osteopontin Deficiency Induces Parathyroid Hormone Enhancement of Cortical Bone Formation

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2132-2140 ◽  
Author(s):  
Keiichiro Kitahara ◽  
Muneaki Ishijima ◽  
Susan R. Rittling ◽  
Kunikazu Tsuji ◽  
Hisashi Kurosawa ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Cortical Bone ◽  
Cancellous Bone ◽  
Wild Type ◽  
Mineral Density ◽  
Cortical Bone Mass ◽  
Intermittent Pth

Intermittent PTH treatment increases cancellous bone mass in osteoporosis patients; however, it reveals diverse effects on cortical bone mass. Underlying molecular mechanisms for anabolic PTH actions are largely unknown. Because PTH regulates expression of osteopontin (OPN) in osteoblasts, OPN could be one of the targets of PTH in bone. Therefore, we examined the role of OPN in the PTH actions in bone. Intermittent PTH treatment neither altered whole long-bone bone mineral density nor changed cortical bone mass in wild-type 129 mice, although it enhanced cancellous bone volume as reported previously. In contrast, OPN deficiency induced PTH enhancement of whole-bone bone mineral density as well as cortical bone mass. Strikingly, although PTH suppressed periosteal bone formation rate (BFR) and mineral apposition rate (MAR) in cortical bone in wild type, OPN deficiency induced PTH activation of periosteal BFR and MAR. In cancellous bone, OPN deficiency further enhanced PTH increase in BFR and MAR. Analysis on the cellular bases for these phenomena indicated that OPN deficiency augmented PTH enhancement in the increase in mineralized nodule formation in vitro. OPN deficiency did not alter the levels of PTH enhancement of the excretion of deoxypyridinoline in urine, the osteoclast number in vivo, and tartrate-resistant acid phosphatase-positive cell development in vitro. These observations indicated that OPN deficiency specifically induces PTH activation of periosteal bone formation in the cortical bone envelope.

scholarly journals Evaluation of bone mineral density (BMD) and indicators of bone turnover in patients with hemophilia

2018 ◽  
Vol 18 (2) ◽  
pp. 206-210 ◽  
Author(s):  
Mehmet Dagli ◽  
Ali Kutlucan ◽  
Sedat Abusoglu ◽  
Abdulkadir Basturk ◽  
Mehmet Sozen ◽  
...  
Keyword(s):  
Bone Mineral Density ◽  
Vitamin D ◽  
Bone Formation ◽  
Bone Mass ◽  
Bone Mineral ◽  
Type I ◽  
Healthy Controls ◽  
Mineral Density ◽  
Lymphocyte Ratio ◽  
Significant Difference

A decrease in bone mass is observed in hemophilic patients. The aim of this study was to evaluate bone mineral density (BMD), parathyroid hormone (PTH), 25-hydroxy vitamin D (vitamin D), and a bone formation and resorption marker, procollagen type I N-terminal propeptide (PINP) and urinary N-terminal telopeptide (uNTX) respectively, in hemophilic patients and healthy controls. Laboratory parameters related to the pathogenesis of bone loss such as neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were also evaluated. Thirty-five men over 18 years of age, with severe hemophilia (A and B) and receiving secondary prophylaxis, were included in the study. The same number of age-, sex-, and ethnicity-matched healthy controls were evaluated. Anthropometric, biochemical, and hormonal parameters were determined in both groups. No significant difference in anthropometric parameters was found between the two groups. The BMD was low in 34% of hemophilic patients. Vitamin D, calcium, and free testosterone levels were significantly lower (p < 0.001, p = 0.011, p < 0.001, respectively), while PTH, PINP, and activated partial thromboplastin time (aPTT) levels were significantly higher (p < 0.014, p = 0.043, p < 0.001, respectively), in hemophilic patients compared to controls. There was no significant difference between the two groups in NLR, PLR, phosphorus, thyroid-stimulating hormone, and uNTX level. The reduction of bone mass in hemophilic patients may be evaluated using the markers of bone formation and resorption, enabling early detection and timely treatment.

Risedronate for the Prevention of Fractures in Postmenopausal Osteoporosis

2002 ◽  
Vol 36 (4) ◽  
pp. 664-670 ◽  
Author(s):  
Jennifer M Sickels ◽  
Chi-Sing Nip
Keyword(s):  
Postmenopausal Osteoporosis ◽  
Bone Fragility ◽  
Mineral Density ◽  
Osteoporosis Therapy ◽  
Treatment Of Osteoporosis ◽  
Medline Search ◽  
Secondary Sources ◽  
Nonvertebral Fractures ◽  
Search Terms ◽  
Increased Risk

OBJECTIVE: To evaluate current scientific literature regarding the efficacy of risedronate in the prevention of vertebral and nonvertebral fractures in women with postmenopausal osteoporosis. DATA SOURCES: Primary research articles were identified by MEDLINE search (1966–May 2001) and through secondary sources. Key search terms were risedronate, postmenopausal osteoporosis, and fractures. DATA SYNTHESIS: Osteoporosis results in a reduction of bone mineral density, increased bone fragility, and increased risk of fractures. The goal of osteoporosis therapy is not only to increase bone mass, but also to reduce the rate of fractures. Risedronate is the newest bisphosphonate to be approved for the prevention and treatment of osteoporosis. An evaluation of clinical trials using risedronate in the treatment of postmenopausal osteoporosis was performed to determine its efficacy at decreasing fracture rates. CONCLUSIONS: Risedronate is an effective and safe option for the treatment of postmenopausal osteoporosis. Risedronate significantly decreases the risk of vertebral and nonvertebral fractures in women who have had ≥1 fractures in the past. More studies are warranted to evaluate the efficacy of risedronate in women without preexisting vertebral fractures.

scholarly journals Porcupine inhibitors impair trabecular and cortical bone mass and strength in mice

2018 ◽  
Vol 238 (1) ◽  
pp. 13-23 ◽  
Author(s):  
Thomas Funck-Brentano ◽  
Karin H Nilsson ◽  
Robert Brommage ◽  
Petra Henning ◽  
Ulf H Lerner ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Formation ◽  
Bone Mass ◽  
Trabecular Bone ◽  
Cortical Bone ◽  
Bone Strength ◽  
Bending Test ◽  
Bone Homeostasis ◽  
Mineral Density

WNT signaling is involved in the tumorigenesis of various cancers and regulates bone homeostasis. Palmitoleoylation of WNTs by Porcupine is required for WNT activity. Porcupine inhibitors are under development for cancer therapy. As the possible side effects of Porcupine inhibitors on bone health are unknown, we determined their effects on bone mass and strength. Twelve-week-old C57BL/6N female mice were treated by the Porcupine inhibitors LGK974 (low dose = 3 mg/kg/day; high dose = 6 mg/kg/day) or Wnt-C59 (10 mg/kg/day) or vehicle for 3 weeks. Bone parameters were assessed by serum biomarkers, dual-energy X-ray absorptiometry, µCT and histomorphometry. Bone strength was measured by the 3-point bending test. The Porcupine inhibitors were well tolerated demonstrated by normal body weight. Both doses of LGK974 and Wnt-C59 reduced total body bone mineral density compared with vehicle treatment (P < 0.001). Cortical thickness of the femur shaft (P < 0.001) and trabecular bone volume fraction in the vertebral body (P < 0.001) were reduced by treatment with LGK974 or Wnt-C59. Porcupine inhibition reduced bone strength in the tibia (P < 0.05). The cortical bone loss was the result of impaired periosteal bone formation and increased endocortical bone resorption and the trabecular bone loss was caused by reduced trabecular bone formation and increased bone resorption. Porcupine inhibitors exert deleterious effects on bone mass and strength caused by a combination of reduced bone formation and increased bone resorption. We suggest that cancer targeted therapies using Porcupine inhibitors may increase the risk of fractures.

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

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.

High bone mass gained by exercise in growing male mice is increased by subsequent reduced exercise

2004 ◽  
Vol 97 (3) ◽  
pp. 806-810 ◽  
Author(s):  
Jian Wu ◽  
Xin Xiang Wang ◽  
Mitsuru Higuchi ◽  
Kazuhiko Yamada ◽  
Yoshiko Ishimi
Keyword(s):  
Bone Mineral Density ◽  
Bone Formation ◽  
Bone Mass ◽  
Exercise Group ◽  
Mineral Apposition Rate ◽  
Male Mice ◽  
Sedentary Control ◽  
Mineral Density ◽  
High Bone Mass ◽  
High Bone

Exercise-induced bone gains are lost if exercise ceases. Therefore, continued exercise at a reduced frequency or intensity may be required to maintain these benefits. In this study, we evaluated whether 4 wk of reduced exercise after 4 wk of running exercise in growing male mice results in the maintenance of high bone mass. Five-week-old mice were divided into the following groups: 1) baseline control; 2) 4-wk control; 3) 4-wk exercise; 4) 8-wk control; 5) 4-wk exercise followed by 4-wk cessation of training; and 6) 4-wk exercise followed by reduced exercise at half the frequency. The regimen consisted of exercise 6 days/wk, and the reduced exercise regimen consisted of running 3 days/wk on a treadmill for 30 min/day, at 12 m/min on a 10° uphill slope. Running exercise significantly increased bone mineral density of the femur, periosteal mineral apposition rate, bone formation rate, percent labeled perimeter at the midfemur, and osteogenic activity of bone marrow cells. However, these parameters declined to the age-matched sedentary control after cessation of training. In contrast, the reduced exercise group had significantly higher mineral apposition rate compared with those of the sedentary control and cessation of training groups. Furthermore, bone mineral density for the reduced exercise group was significantly higher than those for the other groups. These results suggest that the high bone formation gained through exercise can be maintained, and bone mass was further increased by subsequent exercise even if the exercise frequency is reduced.

scholarly journals New Bone Formation with Teriparatide [Human Parathyroid Hormone-(1–34)] Is Not Retarded by Long-Term Pretreatment with Alendronate, Estrogen, or Raloxifene in Ovariectomized Rats

Endocrinology ◽  
2003 ◽  
Vol 144 (5) ◽  
pp. 2008-2015 ◽  
Author(s):  
Yanfei L. Ma ◽  
Henry U. Bryant ◽  
Qingqiang Zeng ◽  
Allen Schmidt ◽  
Jennifer Hoover ◽  
...  
Keyword(s):  
Bone Loss ◽  
Bone Formation ◽  
Formation Rate ◽  
Prior Exposure ◽  
Ovariectomized Rats ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Teriparatide Treatment ◽  
Antiresorptive Agents ◽  
Ovx Rats

With the ready availability of several osteoporosis therapies, teriparatide [human PTH-(1–34)] is likely to be prescribed to postmenopausal women with prior exposure to agents that prevent bone loss, such as bisphosphonates, estrogen, or selective estrogen receptor modulators. Therefore, we evaluated the ability of once daily teriparatide to induce bone formation in ovariectomized (Ovx) rats with extended prior exposure to various antiresorptive agents, such as alendronate (ABP), 17α-ethinyl estradiol (EE), or raloxifene (Ral). Sprague Dawley rats were Ovx and treated with ABP (28 μg/kg, twice weekly), EE (0.1 mg/kg·d), or Ral (1 mg/kg·d) for 10 months before switching to teriparatide 30 μg/kg·d for another 2 months. Analysis of the proximal tibial metaphysis showed that all three antiresorptive agents prevented ovariectomy-induced bone loss after 10 months, but were mechanistically distinct, as shown by histomorphometry. Before teriparatide treatment, ABP strongly suppressed activation frequency and bone formation rate to below levels in other treatment groups, whereas these parameters were not different from sham values for EE or Ral. Trabecular area for ABP, EE, and Ral were greater than that in Ovx controls. However, the trabecular bone effects of ABP were attributed not only to effects on the secondary spongiosa, but also to the preservation of primary spongiosa, which was prevented from remodeling. After 2 months of teriparatide treatment, lumbar vertebra showed relative bone mineral density increases of 18%, 7%, 11%, and 10% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Histomorphometry showed that trabecular area was increased by 105%, 113%, 36%, and 48% for vehicle/teriparatide, ABP/teriparatide, EE/teriparatide, and Ral/teriparatide, respectively, compared with 10 month levels. Teriparatide enhanced mineralizing surface, mineral apposition rate, and bone formation rate in all groups. Compression testing of vertebra showed that teriparatide improved strength (peak load) and toughness in all groups to a proportionately similar extent compared with 10 month levels. These data showed a surprising ability of the rat skeleton to respond to teriparatide despite extensive pretreatment with ABP, EE, or Ral. Therefore, the mature skeleton of Ovx rats remains highly responsive to the appositional effects of teriparatide regardless of pretreatment status in terms of cancellous bone area or rate of bone turnover.

scholarly journals Nutrition as prevention and treatment of osteoporosis

2009 ◽  
pp. S7-S11 ◽  
Author(s):  
M Stránský ◽  
L Ryšavá
Keyword(s):  
Bone Mass ◽  
Randomized Trials ◽  
Bone Structure ◽  
Bone Fractures ◽  
Meta Analysis ◽  
Systemic Disease ◽  
Treatment Of Osteoporosis ◽  
Number Of Factors ◽  
Increased Risk ◽  
Endocrine Factors

Osteoporosis is a systemic disease of the skeleton, characterized by reduction of bone mass and concurrent deterioration of bone structure. Consequently, bones are more fragile, and there is increased risk of fractures. The potential for acquisition of maximum bone mass is influenced by a number of factors. Among those are heredity, sex, nutrition, endocrine factors, mechanical influences and some risk factors. The best documented nutrient for metabolism of bone is calcium. Major role in the pathogenesis of osteoporosis have some micro and macro nutrients, prebiotics, alcohol, alternative diets, starvation and anorexia. Meta analysis of 29 randomized trials showed that supplementation with calcium and vitamin D3 reduces risk of bone fractures by 24 % and significantly reduces loss of bone mass. Osteoporosis has multi factor etiology. Osteoporosis is one of diseases which are influenced by nutrition and life style. It is preventable by means of adequate nutrition and sufficient physical activity.

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