Efficient therapies are available for the treatment of osteoporosis. Anti‐resorptive therapies, including bisphosphonates and denosumab, increase bone mineral density (BMD) and reduce the risk of ...fractures by 20–70%. Bone‐forming or dual‐action treatments stimulate bone formation and increase BMD more than the anti‐resorptive therapies. Two studies have demonstrated that these treatments are superior to anti‐resorptives in preventing fractures in patients with severe osteoporosis. Bone‐forming or dual‐action treatments should be followed by anti‐resorptive treatment to maintain the fracture risk reduction. The BMD gains seen with bone‐forming and dual‐action treatments are greater in treatment‐naïve patients compared to patients pretreated with anti‐resorptive treatments. However, the antifracture efficacy seems to be preserved. Treatment failure will often lead to switch of treatment from orally to parentally administrated anti‐resorptives treatment or from anti‐resorptive to bone‐forming or dual‐action treatment. Osteoporosis is a chronic condition and therefore needs a long‐term management plan with a personalized approach to treatment.
LINKED ARTICLES
This article is part of a themed issue on The molecular pharmacology of bone and cancer‐related bone diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.9/issuetoc
PURPOSE OF REVIEWThe scope of this review was to review the newest developments in the context of the existing knowledge on premenopausal bone fragility. Fragility fractures are common in ...postmenopausal women and men and diagnostic criteria for osteoporosis have been agreed and multiple pharmacological treatments have been developed over the last 25 years. In premenopausal women, fragility fractures and very low bone mass are uncommon and osteoporosis in premenopausal women has therefore attracted much less interest.
RECENT FINDINGSRecent studies have highlighted that lifestyle and dietary habits affect premenopausal bone mass. Bone mass may be improved by sufficient intake of calcium and vitamin D together with increased physical activity in premenopausal women with idiopathic osteoporosis. If pharmacological treatment is needed, teriparatide has been demonstrated to efficiently increase bone mass; however, no fracture studies and no comparative studies against antiresorptive therapies have been conducted. Pregnancy affects bone turnover and mass significantly, but pregnancy-associated osteoporosis is a rare and heterogeneous condition.
SUMMARYThe diagnosis of osteoporosis should only be considered in premenopausal women with existing fragility fractures, diseases or treatments known to cause bone loss or fractures. Secondary causes of osteoporosis should be corrected or treated if possible. The women should be recommended sufficient intake of calcium and vitamin and physical activity. In women with recurrent fractures or secondary causes that cannot be eliminated, for example glucocorticoid or cancer treatment, pharmacological intervention with bisphosphonates or teriparatide (not in the case of cancer) may be considered.
This study aimed to describe clinical outcomes in patients prescribed teriparatide and followed up for 18 months after stopping the drug in real-life conditions. The Extended Forsteo® Observational ...Study analysed incident clinical fractures in 6-month intervals using logistic regression with repeated measures. Changes in back pain (visual analogue scale) and health-related quality of life (HRQoL; EQ-5D questionnaire) were analysed using mixed models for repeated measures. Patients were analysed if they had a post-baseline visit, regardless of whether and for how long they took teriparatide. Of 1531 patients analysed (90.7% female, mean age: 70.3 years), 76 (5.0%) never took teriparatide. Median treatment duration was 23.6 months. The adjusted odds of clinical fracture decreased by 47% in the > 12- to 18-month treatment period (
p
= 0.013) compared with the first 6-month period, with no statistically significant reduction in the > 18- to 24-month interval. The clinical fracture rate remained stable during the 18 months’ post-teriparatide, when approximately 98% of patients took osteoporosis medication (51% bisphosphonates). Clinical vertebral fractures were reduced at every time period compared with the first 6 months. Adjusted mean back pain scores decreased and EQ-5D scores increased significantly at each post-baseline observation. In a real-life clinical setting, the risk of clinical fractures declined during 24 months of teriparatide treatment. This reduction was maintained 18 months after stopping teriparatide. In parallel, patients reported significant improvements in back pain and HRQoL. The results should be interpreted in the context of the non-controlled design of this observational study.
Previous bisphosphonate treatment attenuates the bone-forming effect of teriparatide. We compared the effects of 12 months of romosozumab (AMG 785), a sclerostin monoclonal antibody, versus ...teriparatide on bone mineral density (BMD) in women with postmenopausal osteoporosis transitioning from bisphosphonate therapy.
This randomised, phase 3, open-label, active-controlled study was done at 46 sites in North America, Latin America, and Europe. We enrolled women (aged ≥55 to ≤90 years) with postmenopausal osteoporosis who had taken an oral bisphosphonate for at least 3 years before screening and alendronate the year before screening; an areal BMD T score of −2·5 or lower at the total hip, femoral neck, or lumbar spine; and a history of fracture. Patients were randomly assigned (1:1) via an interactive voice response system to receive subcutaneous romosozumab (210 mg once monthly) or subcutaneous teriparatide (20 μg once daily). The primary endpoint was percentage change from baseline in areal BMD by dual-energy x-ray absorptiometry at the total hip through month 12 (mean of months 6 and 12), which used a linear mixed effects model for repeated measures and represented the mean treatment effect at months 6 and 12. All randomised patients with a baseline measurement and at least one post-baseline measurement were included in the efficacy analysis. This trial is registered with ClinicalTrials.gov, number NCT01796301.
Between Jan 31, 2013, and April 29, 2014, 436 patients were randomly assigned to romosozumab (n=218) or teriparatide (n=218). 206 patients in the romosozumab group and 209 in the teriparatide group were included in the primary efficacy analysis. Through 12 months, the mean percentage change from baseline in total hip areal BMD was 2·6% (95% CI 2·2 to 3·0) in the romosozumab group and −0·6% (−1·0 to −0·2) in the teriparatide group; difference 3·2% (95% CI 2·7 to 3·8; p<0·0001). The frequency of adverse events was generally balanced between treatment groups. The most frequently reported adverse events were nasopharyngitis (28 13% of 218 in the romosozumab group vs 22 10% of 214 in the teriparatide group), hypercalcaemia (two <1% vs 22 10%), and arthralgia (22 10% vs 13 6%). Serious adverse events were reported in 17 (8%) patients on romosozumab and in 23 (11%) on teriparatide; none were judged treatment related. There were six (3%) patients in the romosozumab group compared with 12 (6%) in the teriparatide group with adverse events leading to investigational product withdrawal.
Transition to a bone-forming agent is common practice in patients treated with bisphosphonates, such as those who fracture while on therapy. In such patients, romosozumab led to gains in hip BMD that were not observed with teriparatide. These data could inform clinical decisions for patients at high risk of fracture.
Amgen, Astellas, and UCB Pharma.
This study shows that in postmenopausal women with low bone mineral density, the monoclonal antibody romosozumab, which binds to sclerostin, an osteoblast-activity inhibitor, was associated with ...increased bone mineral density and bone formation and decreased bone resorption.
Osteoporosis is characterized by low bone mass and defects in microarchitecture that are responsible for decreased bone strength and increased risk of fracture.
1
Antiresorptive drugs for osteoporosis increase bone mineral density and prevent the progression of structural damage but may not restore bone structure. Stimulation of bone formation is necessary to achieve improvements in bone mass, architecture, and strength.
Sclerostin, encoded by the gene
SOST,
is an osteocyte-secreted glycoprotein that has been identified as a pivotal regulator of bone formation. By inhibiting the Wnt and bone morphogenetic protein signaling pathways, sclerostin impedes osteoblast proliferation and function, thereby decreasing bone formation. . . .
Osteonecrosis of the jaw (ONJ) has been associated with antiresorptive therapy in both oncology and osteoporosis patients. This debilitating condition is very rare and advances in diagnosis and ...management may now effectively reduce the risk of its development and offer valuable treatment options for affected patients. This paper provides a case-based review of ONJ and application of the International Task Force on ONJ (referred to as the "Task Force") recommendations for the diagnosis and management of ONJ. The Task Force was supported by 14 international societies and achieved consensus from representatives of these multidisciplinary societies on key issues pertaining to the diagnosis and management of ONJ. The frequency of ONJ in oncology patients receiving oncology doses of bisphosphonate (BP) or denosumab is estimated at 1%-15%, and the frequency in the osteoporosis patient population receiving much lower doses of BP or denosumab is estimated at 0.001%-0.01%. Although the diagnosis of ONJ is primarily clinical, imaging may be helpful in confirming the diagnosis and staging. In those with multiple risk factors for ONJ for whom major invasive oral surgery is being planned, interruption of BP or denosumab therapy (in cancer patients) is advised, if possible, before surgery, until the surgical site heals. Major oral surgery in this context could include multiple extractions if surgical extractions are required, not simple forceps extractions. ONJ development may be reduced by optimizing oral hygiene and postoperatively using topical and systemic antibiotics as appropriate. Periodontal disease should be managed before starting oncology doses of BP or denosumab. Local debridement may be successful in disease unresponsive to conservative therapy. Successful surgical intervention has been reported in those with stage 3 disease; less severe disease is best managed conservatively. Teriparatide may be helpful in healing ONJ lesions and may be considered in osteoporosis patients at a high fracture risk in the absence of contraindications. Resumption of BP or denosumab therapy following healing of ONJ lesions is recommended, and there have not been reports of subsequent local recurrence.
Liraglutide, a glucagon-like peptide-1 receptor agonist, has well known beneficial effects on glucose metabolism, and animal studies indicate that liraglutide also affects bone turnover by decreasing ...bone resorption. The primary objective of the study was to investigate the effect of liraglutide on bone turnover in patients with T2D.
The study was a randomized, double-blinded, clinical trial. Sixty participants with T2D were randomized to treatment with liraglutide 1.8 mg daily or placebo for 26 weeks. The primary endpoint was change in p-collagen I cross-linked C-terminal telopeptide (p-CTX).
P-CTX increased in patients treated with liraglutide by 0.07 (0.03; 0.10) μg/L (p < 0.001) and in patients treated with placebo by 0.03 (0.00; 0.06) μg/L (p = 0.04), however, changes were not different between the groups (p = 0.16). Weight decreased in patients treated with liraglutide from baseline to week four (p < 0.001) and remained stable thereafter. P-procollagen type 1 N-terminal propeptide (P1NP) decreased in patients treated with liraglutide from baseline to week four (p < 0.01), increased between weeks 4 and 13 (p = 0.03), and remained elevated thereafter. Weight and p-P1NP did not change in patients treated with placebo. Hip bone mineral density (BMD) decreased in placebo treated patients from baseline to end of study, whereas no changes were seen in patients treated with liraglutide (p = 0.01 difference between groups).
Liraglutide treatment for 26 weeks did not affect bone resorption and preserved hip BMD despite weight loss in patients with T2D, suggesting that liraglutide has some antiresorptive effect.
•Liraglutide treatment of patients with type 2 diabetes for 26 weeks did not affect bone resorption, despite weight loss•Bone formation markers decreased during weight loss but increased during weight maintenance in the liraglutide treated group•Liraglutide treatment preserved hip bone mineral density compared with placebo
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