Current approaches to osteoporosis treatment

Lim, Sian Yik; Bolster, Marcy B.

doi:10.1097/bor.0000000000000169

Cited by 59 publications

(41 citation statements)

References 57 publications

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“…Although a number of efficient therapeutic agents are available now [3], parathyroid hormone (PTH1-84) or the synthetic peptide PTH1-34 (teriparatide) recapitulating the effects of PTH is the only agent that induces anabolic action of bone formation [4,5]. Molecular mechanisms of the anabolic action of PTH have been investigated from various aspects [6][7][8].…”

Section: Introductionmentioning

confidence: 99%

PTH-Induced Osteoblast Proliferation Requires Upregulation of the Ubiquitin-Specific Peptidase 2 (Usp2) Expression

et al. 2015

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Osteoporosis is a common disease that increases individual's fragility fracture risk. PTH is the only therapeutic agent for severe osteoporosis that requires anabolic action of bone formation. Although a part of the PTH actions is explained by increased proliferation of osteoblastic precursor cells, the mechanisms involved in the proliferation of osteoblastic cells by PTH have not been clarified yet. Therefore, in this study, we investigated the effects of PTH on gene expression in the cultured osteoblastic MC3T3-E1 cells, and found that the ubiquitin-specific peptidase 2 (Usp2) may be one of the direct target genes of PTHR signaling. Usp2 is a deubiquitination enzyme targeting various factors including CyclinD1 in cancer cells and PTH receptor 1 in osteoblasts. We confirmed that consistent induction of Usp2 expression peaked at 1 h by PTH1-34 (teriparatide) in MC3T3-E1 cells and primary calvarial osteoblasts. Among the three known splicing variants of the Usp2, we found the isoforms 1 and 2 are predominantly expressed in osteoblasts. Live-imaging analysis of the Fucci-transgenic mouse-derived primary osteoblasts indeed demonstrated that Usp2 is required for the PTH1-34-induced osteoblast proliferation. Western blotting analysis of the CyclinD1 indicated that Usp2 knock-down influences the paradoxical changes of CyclinD1 protein levels in this condition. Our data indicate that Usp2 is required for the PTH1-34-induced proliferation of osteoblasts.

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Section: Introductionmentioning

confidence: 99%

PTH-Induced Osteoblast Proliferation Requires Upregulation of the Ubiquitin-Specific Peptidase 2 (Usp2) Expression

et al. 2015

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“…Advances in knowledge of bone biology in recent years have contributed to major therapeutic advances in OP treatments. 1 …”

Section: Introductionmentioning

confidence: 99%

Two-year clinical outcome of denosumab treatment alone and in combination with teriparatide in Japanese treatment-naive postmenopausal osteoporotic women

et al. 2017

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This randomized prospective study aimed to evaluate the clinical outcome of denosumab treatment alone and in combination with teriparatide in treatment-naive postmenopausal Japanese female patients with osteoporosis. Thirty patients were randomly assigned to two groups: (1) denosumab group (denosumab alone, n=13); and (2) combination group (denosumab+teriparatide, n=17). Serum bone-specific alkaline phosphatase (BAP), serum tartrate-resistant acid phosphatase (TRACP)-5b, urinary cross-linked N-terminal telopeptides of type I collagen (NTX), and bone mineral density (BMD) of L1–4 lumbar vertebrae (L-BMD) and bilateral total hips (H-BMD) were determined at the first visit and at various time points up to 24 months post-treatment to determine percentage changes. Serum TRACP-5b and urinary NTX were equally suppressed in both groups and maintained at low levels, with slight increases at 12, 18 and 24 months. BAP was significantly decreased in both groups from 4 to 24 months, with significant differences between the groups at 4, 8 and 15 months (P<0.05). L-BMD was significantly increased at most time points in both groups, with a significant difference between the combination group and denosumab group at 24 months (17.2% increase versus 9.6% increase; P<0.05). There was no significant difference in H-BMD between the two groups, although the levels tended to be higher in the combination group than in the denosumab group (9.5% increase versus 5.6% increase). These findings suggest that denosumab+teriparatide combination therapy may represent an important treatment for primary osteoporotic patients at high risk of vertebral fracture.

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“…(1,2 ) Bisphosphonates remain first-line treatment for osteoporosis, however these medications have safety concerns which limit long-term use. (3) …”

Section: Introductionmentioning

confidence: 99%

Nitrate Medications, Fractures, and Change in Bone Mineral Density in Postmenopausal Women: Results from the Women's Health Initiative

Golchin

Hohensee

LaCroix

et al. 2016

Journal of Bone and Mineral Research

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Nitrate medications may increase bone mineral density (BMD), although information on fracture outcomes is sparse. We examined the association of nitrate medications with fractures (hip, wrist/arm and total fractures) and changes in BMD (hip, spine and whole body) in the Women’s Health Initiative (WHI) Clinical Trials and Observational Study. A total of 139,211 postmenopausal women 50 to 79 years old without history of hip fracture were included in this prospective study. Medication use was ascertained directly from drug containers at baseline during in-person interviews in 1993-1998. Exposure measures included any use (use/non-use), type of nitrate (as-needed, maintenance) and duration of use (≤ 5 years, > 5 years). We used separate multivariable Cox proportional hazard models to analyze associations between each exposure and fracture outcome, with results presented as hazard ratios (HRs) and 95% confidence intervals (CI). Multivariable linear regression models were used to examine 3 and 6-year changes in BMD. At baseline, 1.2% (n=1647) women were using a nitrate. During the mean (SD) follow-up of 7.7 (1.5) years through 2005, women experienced 1582 hip fractures, 5156 wrist or arm fractures, and 22, 589 total fractures. After adjustment for confounders, nitrate use was not statistically associated with risk for hip (HR, 0.81; 95% CI, 0.56–1.18), wrist/arm (HR, 0.95; 95% CI, 0.74-1.23) or total fractures (HR, 0.96; 95% CI, 0.85-1.08). As-needed nitrate use, but not maintenance therapy, was associated with a lower risk of total fractures (HR, 0.77; 95% CI, 0.62–0.95) and wrist/arm fractures (HR, 0.57; 95% CI, 0.34-0.98). Nitrate use was not associated with 3 or 6-year changes in BMD at any site. We conclude that any nitrate use was not significantly associated with lower risk of fractures or higher BMD, however as-needed nitrates were associated with lower risks of total and wrist/arm fractures.

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Current approaches to osteoporosis treatment

Cited by 59 publications

References 57 publications

PTH-Induced Osteoblast Proliferation Requires Upregulation of the Ubiquitin-Specific Peptidase 2 (Usp2) Expression

PTH-Induced Osteoblast Proliferation Requires Upregulation of the Ubiquitin-Specific Peptidase 2 (Usp2) Expression

Two-year clinical outcome of denosumab treatment alone and in combination with teriparatide in Japanese treatment-naive postmenopausal osteoporotic women

Nitrate Medications, Fractures, and Change in Bone Mineral Density in Postmenopausal Women: Results from the Women's Health Initiative

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