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Background and Objective: Abaloparatide, an anabolic osteoporosis treatment administered by subcutaneous (SC) injection, increases bone mineral density (BMD) and reduces fracture risk in postmenopausal women with osteoporosis. The abaloparatide-solid Microstructured Transdermal System [abaloparatide-sMTS (Kindeva, St Paul, MN, USA)], which delivers abaloparatide intradermally, is in development to provide an alternative method for abaloparatide delivery. The objective of this study was to evaluate the ability of subjects to self-administer abaloparatide-sMTS, based on pharmacokinetic and pharmacodynamic markers., Methods: In this single-arm, open-label, Phase 1b study, 22 healthy postmenopausal women aged 50-85 years with low BMD were trained to self-administer abaloparatide-sMTS 300 μg once daily to the thigh for 5 min for 29 days. The primary endpoint was systemic exposure to abaloparatide. Secondary endpoints included percent change from baseline in serum procollagen type I N-terminal propeptide (s-PINP), patient experience, and safety., Results: All 22 subjects completed the study. At baseline, mean age was 65.2 years, mean total hip T-score was - 1.32, and mean lumbar spine T-score was - 1.98. On Day 1, the median time to reach maximum concentration (T max ) for abaloparatide-sMTS was 0.33 h and geometric mean (CV %) maximum concentration (C max ) and area under the concentration-time curve from time 0 to the time of the last quantifiable concentration (AUC 0-t ) were 447 (38.0) pg/mL and 678 (45.3) pg·h/mL, respectively; the pharmacokinetic profile was similar on Days 15 and 29. Median percentage change in s-PINP was 45.4% and 64.4% at Days 15 and 29, respectively. The most common adverse events (AEs) were application site erythema, pain, and swelling, which were mostly of mild or moderate severity. No AEs led to study drug withdrawal and no serious AEs were reported. The success rate for self-administration at first application was 99.7%, and subject acceptability was high (~ 4.5 on a 5-point Likert Scale)., Conclusions: Subjects successfully self-administered abaloparatide-sMTS, which provided a consistent pharmacokinetic profile over 29 days and produced s-PINP increases from baseline similar to that observed in the pivotal trial with abaloparatide-SC. Observed patient experience along with the clinical data support continued clinical development of abaloparatide-sMTS., Trial Registration Number: NCT04366726, Date of registration 04/29/2020, retrospectively registered.

Context: Abaloparatide is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture., Objectives: We assessed the cardiovascular safety profile of abaloparatide., Design: Review of heart rate (HR), blood pressure (BP), and cardiovascular-related adverse events (AEs), including major adverse cardiovascular events (MACEs) and heart failure (HF) from: (a) ACTIVE (NCT01343004), a phase 3 trial that randomized 2463 postmenopausal women with osteoporosis to abaloparatide, teriparatide, or placebo for 18 months; (b) ACTIVExtend (NCT01657162), where participants from the abaloparatide and placebo arms received alendronate for 2 years; and (c) a pharmacology study in 55 healthy adults., Results: Abaloparatide and teriparatide transiently increased HR relative to placebo. Following first dose, mean (standard deviation [SD]) HR change from pretreatment to 1 hour posttreatment was 7.9 (8.5) beats per minute (bpm) for abaloparatide, 5.3 (7.5) for teriparatide, and 1.2 (7.1) for placebo. A similar pattern was observed over subsequent visits. In healthy volunteers, HR increase resolved within 4 hours. The corresponding change in mean supine systolic and diastolic BP 1 hour posttreatment was -2.7/-3.6 mmHg (abaloparatide), -2.0/-3.6 (teriparatide), and -1.5/-2.3 (placebo). The percentage of participants with serious cardiac AEs was similar among groups (0.9%-1.0%). In a post hoc analysis, time to first incidence of MACE + HF was longer with abaloparatide (P = 0.02 vs placebo) and teriparatide (P = 0.04 vs placebo)., Conclusions: Abaloparatide was associated with transient increases in HR and small decreases in BP in postmenopausal women with osteoporosis, with no increase in risk of serious cardiac AEs, MACE, or HF., (© Endocrine Society 2020.)

Background: The validation of bone mineral density (BMD) as a surrogate outcome for fracture would allow the size of future randomised controlled osteoporosis registration trials to be reduced. We aimed to determine the association between treatment-related changes in BMD, assessed by dual-energy x-ray absorptiometry, and fracture outcomes, including the proportion of treatment effect explained by BMD changes., Methods: We did a pooled analysis of individual patient data from multiple randomised placebo-controlled clinical trials. We included data from multicentre, randomised, placebo-controlled, double-blind trials of osteoporosis medications that included women and men at increased osteoporotic fracture risk. Using individual patient data for each trial we calculated mean 24-month BMD percent change together with fracture reductions and did a meta-regression of the association between treatment-related differences in BMD changes (percentage difference, active minus placebo) and fracture risk reduction. We also used individual patient data to determine the proportion of anti-fracture treatment effect explained by BMD changes and the BMD change needed in future trials to ensure fracture reduction efficacy., Findings: Individual patient data from 91 779 participants of 23 randomised, placebo-controlled trials were included. The trials had 1-9 years of follow-up and included 12 trials of bisphosphonate, one of odanacatib, two of hormone therapy (one of conjugated equine oestrogen and one of conjugated equine oestrogen plus medroxyprogesterone acetate), three of PTH receptor agonists, one of denosumab, and four of selective oestrogen receptor modulator trials. The meta-regression revealed significant associations between treatment-related changes in hip, femoral neck, and spine BMD and reductions in vertebral (r 2 0·73, p<0·0001; 0·59, p=0·0005; 0·61, p=0·0003), hip (0·41, p=0·014; 0·41, p=0·0074; 0·34, p=0·023) and non-vertebral fractures (0·53, p=0·0021; 0·65, p<0·0001; 0·51, p=0·0019). Minimum 24-month percentage changes in total hip BMD providing almost certain fracture reductions in future trials ranged from 1·42% to 3·18%, depending on fracture site. Hip BMD changes explained substantial proportions (44-67%) of treatment-related fracture risk reduction., Interpretation: Treatment-related BMD changes are strongly associated with fracture reductions across randomised trials of osteoporosis therapies with differing mechanisms of action. These analyses support BMD as a surrogate outcome for fracture outcomes in future randomised trials of new osteoporosis therapies and provide an important demonstration of the value of public access to individual patient data from multiple trials., Funding: Foundation for National Institutes of Health., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Teriparatide (rhPTH[1-34]), a bone-forming agent for the treatment of osteoporosis, increases bone mineral density in men and women, and reduces the risk of fractures in women with osteoporosis. However, fracture efficacy has not yet been confirmed in men. Further, there is limited information on the effect of withdrawal of teriparatide. The purpose of this manuscript is to report on bone mineral density and vertebral fracture incidence during a 42-month observation period, from the baseline of the previously reported treatment study in men [1] through 30 months of posttreatment follow-up. Three hundred fifty-five men who were treated with once-daily self-injections of either placebo or 20 or 40 microg of teriparatide participated in the follow-up study. Bone mineral density gradually decreased following discontinuation of teriparatide therapy. However, the lumbar spine and total hip values remained significantly higher than baseline after 30 months of follow-up (p< or =0.001). Antiresorptive treatment prevented the decline and tended to further increase bone mineral density. Lateral thoracic lumbar radiographs obtained at baseline and 18 months after discontinuation of teriparatide were available for 279 men. Of these men, 11.7% assigned to placebo, 5.4% treated with teriparatide 20 microg, and 6.0% treated with teriparatide 40 microg had an incident vertebral fracture. In the combined teriparatide treated groups vs placebo, the risk of vertebral fracture was reduced 51% (nonsignificant, p=0.07). The incidence of moderate or severe fractures was significantly reduced by 83% (p=0.01). In conclusion, men who received teriparatide and who may have received follow-up antiresorptive therapy had a decreased risk of moderate and severe vertebral fractures.

Background: Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown., Methods: We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry., Results: New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache)., Conclusions: Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.

Background: In postmenopausal women, raloxifene hydrochloride has favorable effects on bone and lipid metabolism and does not stimulate reproductive tissues. The studies reported herein evaluated the long-term (3-year) effects of raloxifene treatment on bone mineral density (BMD), serum lipid levels, and drug tolerability in healthy postmenopausal women., Methods: A total of 1145 healthy European and North American postmenopausal women aged 45 through 60 years were enrolled in 2 parallel, double-blind, randomized, placebo-controlled trials of identical design and randomly assigned to receive raloxifene hydrochloride, 30, 60, or 150 mg, or placebo daily; all groups received 400 to 600 mg of elemental calcium. Assessments included measurements for BMD by dual-energy x-ray absorptiometry, markers of bone turnover, and serum lipid levels., Results: Lumbar spine BMD changed from baseline to 36 months as follows: placebo (mean percentage change + SE), -1. 32% +0.22%; raloxifene, 30 mg, 0.71% +0.23%; raloxifene, 60 mg, 1. 28% +0.23%; and raloxifene, 150 mg, 1.20% +0.24%. Comparable BMD changes were observed in the hip and total body. Biochemical markers of bone turnover were suppressed by raloxifene to normal premenopausal ranges through 3 years. Serum low-density lipoprotein cholesterol was reduced 7% to 12% below baseline through 3 years. Study withdrawals due to any reason (37%) and withdrawals due to adverse events (14%) were not different among groups. The only significant adverse effect of therapy was hot flashes (25% in the 60-mg raloxifene group vs 18% in the placebo group); hot flashes were typically reported as mild and were not associated with study withdrawal (1.7% for 60-mg raloxifene vs 2.4% for placebo)., Conclusions: Raloxifene preserves BMD at important skeletal sites, lowers serum low-density lipoprotein cholesterol levels, and has a tolerability profile comparable to placebo. These results indicate a favorable benefit-risk profile of raloxifene for long-term use in healthy postmenopausal women. Arch Intern Med. 2000;160:3444-3450.

Background: Long-term estrogen therapy can reduce the risk of osteoporotic fracture and cardiovascular disease in postmenopausal women. At present, however, these beneficial effects are not separable from undesirable stimulation of breast and endometrial tissues., Methods: We studied the effect of raloxifene, a nonsteroidal benzothiophene, on bone mineral density, serum lipid concentrations, and endometrial thickness in 601 postmenopausal women. The women were randomly assigned to receive 30, 60, or 150 mg of raloxifene or placebo daily for 24 months., Results: The women receiving each dose of raloxifene had significant increases from base-line values in bone mineral density of the lumbar spine, hip, and total body, whereas those receiving placebo had decreases in bone mineral density. For example, at 24 months, the mean (+/-SE) difference in the change in bone mineral density between the women receiving 60 mg of raloxifene per day and those receiving placebo was 2.4+/-0.4 percent for the lumbar spine, 2.4+/-0.4 percent for the total hip, and 2.0+/-0.4 percent for the total body (P<0.001 for all comparisons). Serum concentrations of total cholesterol and low-density lipoprotein cholesterol decreased in all the raloxifene groups, whereas serum concentrations of high-density lipoprotein cholesterol and triglycerides did not change. Endometrial thickness was similar in the raloxifene and placebo groups at all times during the study. The proportion of women receiving raloxifene who reported hot flashes or vaginal bleeding was not different from that of the women receiving placebo., Conclusions: Daily therapy with raloxifene increases bone mineral density, lowers serum concentrations of total and low-density lipoprotein cholesterol, and does not stimulate the endometrium.

Although daily injections of parathyroid hormone (PTH) can rapidly reverse estrogen-deficiency bone loss in rats, PTH treatment of osteoporotic humans has to date produced more modest increases in bone mass. To explore the reasons for this important difference, we evaluated the dose- and time-dependence of human PTH 1-84 treatment effects on bone mass and biochemical markers of bone metabolism in rats with estrogen-deficiency bone loss. The highest doses of PTH increased spinal, femoral, and total skeletal mass to supra-normal levels and stimulated cortical endosteal bone formation. Spine and whole skeleton mass and density increased rapidly at first, but then increased more slowly; the rate of change decreased significantly (p < 0.01) during continued treatment with the highest doses of PTH. The effects of PTH treatment on biochemical markers also were both dose-dependent and time-dependent. Serum osteocalcin, a marker of osteoblast function, increased with the highest doses of PTH (p < 0.001), but reached an early plateau and later returned toward baseline. Urinary excretion of pyridinolines, a marker of osteoclast function, increased in a time-dependent fashion throughout treatment (p < 0.001). Serum 1,25(OH)2 vitamin D levels increased in a dose-related fashion, but then decreased toward control levels despite continued treatment. We demonstrate that both osteoblast and osteoclast function are increased during daily PTH therapy in the rat. The pattern of response depends on both the dose of PTH and the duration of therapy. These dose- and time-related effects should be taken into account when designing experimental PTH treatments for osteoporosis, and they deserve intensive study.

We evaluated the precision and accuracy of dual-energy x-ray bone densitometry (DXA) in 38 male and female rats aged 1-10 months. The coefficients of variation (CV) estimated from same-day paired measurements of bone mineral content (BMC) were 1.26% at the lumbar spine and 0.69% at the whole skeleton, and the corresponding CV for BMC corrected for projected bone area (i.e., bone mineral density, BMD) were 0.57 and 0.66%. BMC, measured in vivo, correlated closely with the subsequently determined ash weights (spine r2 = 0.94, whole-skeleton r2 = 0.97). The long-term CV for BMC measurements, assessed by measuring a frozen animal daily for 4 weeks, were 1.28% for the spine and 1.03% for the whole skeleton; for BMD the corresponding CV were 0.88 and 1.15%. To examine the utility of serial DXA measurements we followed female rats subjected to ovariectomy (OVX) or sham operation at 10 months of age and male rats given daily subcutaneous injections of hPTH-(1-34) or vehicle starting at 10 months of age every 3 weeks for 15 weeks. In the OVX rats a progressive decrease in spine BMC was observed that was most rapid during the first 6 weeks. By 15 weeks the mean spine BMC decreased by 17% in the OVX rats (p < 0.007 versus sham operation). OVX did not affect the accuracy of DXA measurements as assessed by comparison with the ash weight at the end of the 15 week study. PTH treatment increased spine BMC by a mean of 32% and increased whole-skeleton BMC by a mean of 19% within 15 weeks.(ABSTRACT TRUNCATED AT 250 WORDS)

We examined the effect of intermittent administration of bovine parathyroid hormone (1-34) (bPTH) on spinal bone mineral content (BMC) and bone mineral density (BMD), serum 1,25-dihydroxyvitamin D concentrations, and serum markers of osteoblast function in senile male and female rats (23 and 24 months of age, respectively). Sexually mature young (3 month) male rats were similarly treated for comparison. bPTH administration increased serum osteocalcin concentrations without changing serum inorganic phosphate or calcium concentrations in either group of old animals. In young animals, PTH administration increased the serum calcium and inorganic phosphate concentrations significantly (p less than 0.05), although values remained within the normal range. In the vehicle-treated male rats, serum 1,25-dihydroxyvitamin D concentrations were lower in the senile than in the young animals (18 +/- 5 versus 47 +/- 6 pg/ml, p less than 0.05). PTH administration resulted in significantly increased serum 1,25-dihydroxyvitamin D concentrations in the senile and young male animals (both, p less than 0.05) and the final mean serum 1,25-dihydroxyvitamin D concentrations were not statistically different (68 +/- 9 versus 85 +/- 6 pg/ml respectively; p = NS). Serum 1,25-dihydroxyvitamin D concentrations were significantly (p less than 0.05) higher in the PTH-treated senile female rats than the sex-matched, vehicle-treated controls. The pretreatment spinal BMC and BMD as assessed by dual-energy x-ray absorptiometry (DEXA) were significantly higher in the senile male animals than in the young animals. Spinal BMC and BMD decreased in the vehicle-treated senile male rats (p less than 0.05) over the 3 weeks of the study despite a gain in weight.(ABSTRACT TRUNCATED AT 250 WORDS)

Of 118 consecutive white patients referred for asymptomatic primary hyperparathyroidism, the diagnosis was clinically confirmed in 100, of whom 85 adults had a serum calcium less than 3.0 mM (12 mg/dl) and no skeletal, rheumatic, or significant neuropsychiatric symptoms, azotemia, or other significant illnesses. Among these 85, 68 had both asymptomatic and medically uncomplicated hyperparathyroidism, whereas 17 had historical, radiographic, or ultrasonic evidence of renal stone disease. The 20% with past or present renal calculi concentrated their urine significantly better than the 68 others (p = 0.05), but these two groups were otherwise not distinguished by the tests we performed, so all 85 patients were analyzed together. Systolic and diastolic blood pressures were normal, but premature osteopenia and/or impaired renal function were present in 29-36% of the patients. Micrometer measurements of metacarpal radiographs and 125I photon absorptiometry at the shaft of the radius revealed cortical osteopenia. Osteopenia was equally significant in the distal radius (cortical plus trabecular bone). These quantitative measurements were superior to routine bone radiography, and ROC analysis showed that 125I absorptiometry at either site was superior (p less than 0.01) to metacarpal cortex measurements for detecting premature osteopenia, which was present in more than a third of these patients. Creatinine clearances (24 h) and maximum urine concentrating capacity (overnight dehydration plus the synthetic vasopressin analog DDAVP) were each significantly reduced, despite all patients' normal BUN and serum creatinine levels. Sequential performance of a 24 h creatinine clearance and a urine concentration test revealed abnormalities in the renal function of 27 of 74 patients (36%), with a specificity of 95% and a higher sensitivity than either test alone (27-29%).(ABSTRACT TRUNCATED AT 250 WORDS)

Summary: Abaloparatide increased ultradistal radius bone mineral density (BMD) in the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Over the subsequent 24 months in ACTIVExtend, ultradistal radius BMD gains were maintained with alendronate. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE. Introduction: Abaloparatide (ABL) increased femoral neck, total hip, and lumbar spine bone mineral density (BMD) in postmenopausal women with osteoporosis and decreased the risk of vertebral and nonvertebral fractures in ACTIVE. Effects on fracture risk and BMD were maintained subsequently with alendronate (ALN) in ACTIVExtend. In a prespecified subanalysis of ACTIVE, ABL also increased BMD at the ultradistal radius. Our objective was to determine the efficacy of ABL followed by ALN vs placebo (PBO) followed by ALN on forearm BMD and fracture risk over 43 months in ACTIVExtend. Methods: Ultradistal and 1/3 radius BMD (ACTIVE baseline to month 43) were measured (ABL/ALN, n = 213; PBO/ALN, n = 233). Wrist fracture rates were estimated for the ACTIVExtend intent-to-treat population (ABL/ALN, n = 558; PBO/ALN, n = 581) by Kaplan-Meier (KM) method. Results: At cumulative month 25, mean increase from ACTIVE baseline in ultradistal radius BMD was 1.1% (standard error, 0.49%) with ABL/ALN vs − 0.8% (0.43%) with PBO/ALN (P < 0.01). BMD increases with ABL were maintained with ALN through month 43 in ACTIVExtend. BMD decreases at the 1/3 radius in ACTIVE (similar with ABL and PBO) were maintained through 24 months of ALN treatment in ACTIVExtend. Wrist fractures over 43 months occurred in 15 women with ABL/ALN (KM estimate, 2.8%) and 20 with PBO/ALN (KM estimate, 3.6%) (HR = 0.77, 95% CI 0.39, 1.50; P = not significant). Conclusion: Ultradistal radius BMD gains following treatment with ABL in ACTIVE were maintained over 24 months of ALN treatment in ACTIVExtend. Conversely, 1/3 radius BMD remained stable during ALN treatment in ACTIVExtend after decreasing during ACTIVE. Trial registration: ClinicalTrials.gov: NCT01657162 submitted July 31, 2012 [ABSTRACT FROM AUTHOR]

Summary: Early PINP changes correlate with 18-month lumbar spine BMD changes and the correlation was greater with abaloparatide versus teriparatide. The uncoupling index was similar between the two agents.Introduction: We evaluated the relationship between early PINP changes and subsequent changes in spine BMD following abaloparatide and teriparatide treatments. We also explored the use of an "uncoupling index" (UI), the balance between bone formation and bone resorption, which we hypothesised would be similar in response to these treatment groups.Methods: Blood samples were taken for measurement of bone turnover markers (BTMs) s-PINP and s-CTX at baseline, 1, 3, 6, 12, and 18 months from 189 abaloparatide patients and 227 teriparatide patients randomly selected from all participants who completed the study. BMD was measured by DXA at baseline, 6, 12, and 18 months. Correlations were calculated between log ratio of BTMs from baseline to 3 months and percent change from baseline in BMD at 18 months. A UI was calculated using log transformation and subtraction of the standard deviate for s-CTX from the standard deviate for s-PINP for each patient.Results: Early BTM changes were associated with subsequent BMD changes for both treatments. Pearson correlations for the log ratio of PINP over baseline at 3 months and BMD percent change from baseline at 18 months were larger (P < 0.0001) with abaloparatide (r = 0.561) than teriparatide (r = 0.198). The mean UI at 1 month was greater for abaloparatide versus teriparatide (1.743 and 1.493, respectively; P = 0.03) but was similar at 3 months or later time points.Conclusions: Early s-PINP changes correlate with percentage change in lumbar spine BMD 18 months after treatment with both abaloparatide and teriparatide, though the correlation with abaloparatide was greater. The UI was similar between abaloparatide and teriparatide suggesting that the balance between formation and resorption markers was similar. [ABSTRACT FROM AUTHOR]

This review summarizes the available evidence-based data that form the basis for therapeutic intervention and covers the current status of glucocorticoid-induced osteoporosis (GIOP) management, regulatory requirements, and risk-assessment options. Glucocorticoids are known to cause bone loss and fractures, yet many patients receiving or initiating glucocorticoid therapy are not appropriately evaluated and treated. An European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis workshop was convened to discuss GIOP management and to provide a report by a panel of experts. An expert panel reviewed the available studies that discussed approved therapeutic agents, focusing on randomized and controlled clinical trials reporting on bone mineral density and/or fracture risk of at least 48 weeks' duration. There is no evidence that GIOP and postmenopausal osteoporosis respond differently to treatments. The FRAX algorithm can be adjusted according to glucocorticoid dose. Available antiosteoporotic therapies such as bisphosphonates and teriparatide are efficacious in GIOP management. Several other agents approved for the treatment of postmenopausal osteoporosis may become available for GIOP. It is advised to stop antiosteoporotic treatment after glucocorticoid cessation, unless the patient remains at increased risk of fracture. Calcium and vitamin D supplementation as an osteoporosis-prevention measure is less effective than specific antiosteoporotic treatment. Fracture end-point studies and additional studies investigating specific subpopulations (pediatric, premenopausal, or elderly patients) would strengthen the evidence base and facilitate the development of intervention thresholds and treatment guidelines. [ABSTRACT FROM AUTHOR]

Osteoporotic fracture healing is critical to clinical outcome in terms of functional recovery, morbidity, and quality of life. Osteoporosis treatments may affect bone repair, so insights into their impact on fracture healing are important. We reviewed the current evidence for an impact of osteoporosis treatments on bone repair. Treatment with bisphosphonate in experimental models is associated with increased callus size and mineralization, reduced callus remodeling, and improved mechanical strength. Local and systemic bisphosphonate treatment may improve implant fixation. No negative impact on fracture healing has been observed, even after major surgery or when administered immediately after fracture. Experimental data for denosumab and raloxifene suggest no negative implications for bone repair. The extensive experimental results for teriparatide indicate increased callus formation, improved biomechanical strength, and greater external callus volume and total bone mineral content and density. Case reports and a randomized trial have produced mixed results but are consistent with a positive impact of teriparatide on clinical fracture healing. Studies with strontium ranelate in models of fracture healing indicate that it is associated with improved bone microstructure, callus volume, and biomechanical properties. Finally, there is experimental evidence for a beneficial effect of some of the agents currently being developed for osteoporosis, notably sclerostin antibody and DKK1 antibody. There is currently no evidence that osteoporosis treatments are detrimental for bone repair and some promising experimental evidence for positive effects on healing, notably for agents with a bone-forming mode of action, which may translate into therapeutic applications. [ABSTRACT FROM AUTHOR]

To evaluate the usability of abaloparatide solid microstructured transdermal system (ABL-sMTS) as measured by overall persistence, satisfaction, and acceptability of study therapy. ABL-sMTS usability was measured by user error incidence, satisfaction, and acceptability, by subject diary as well as total used ABL-sMTS returned at each study visit. Conclusions This is the first evaluation of a novel transdermal, self-administered, multi-dose regimen of ABL-sMTS in PMP women with low BMD. [Extracted from the article]