Skeletal Consequences of Hormone Therapy Discontinuance: A Systematic Review

Simon, James A.; Wehren, Lois E.; Ascott-Evans, Brynne; Omizo, Molly; Silfen, Sheryl L.; Lombardi, Antonio

doi:10.1097/01.ogx.0000189152.95070.f8

Cited by 17 publications

(6 citation statements)

References 35 publications

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“…In the prevention-HT arm, bone turnover is high after gonadectomy[21]. High turnover is also observed in humans immediately after menopause or gonadectomy [25]. In both humans and rodents, turnover rates decline with time [21–23, 26].…”

Section: Discussionmentioning

confidence: 99%

“…DHT treatment for 6 weeks is sufficient time to observe response to therapy, as major effects of androgen depletion and/or replacement on bone metabolism have been observed in rodents in just 3 weeks [24]. High turnover with rapid bone loss and low turnover with slow bone loss are established states of bone turnover that occur immediately or several months after gonadectomy in both humans and rodents [21–23, 25, 26]. Thus, after the two month delay, the high bone turnover typically observed after ORX has stabilized to a lower turnover state (LT).…”

Section: Methodsmentioning

confidence: 99%

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Androgen prevents hypogonadal bone loss via inhibition of resorption mediated by mature osteoblasts/osteocytes

Wiren

Zhang

Olson

et al. 2012

Bone

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Androgen receptor (AR) is expressed throughout the osteoblast lineage. Two different AR transgenic families (AR2.3-tg and AR3.6-tg mice) demonstrating overlapping and distinct expression profiles were employed to assess the effects of enhanced androgen sensitivity to ameliorate hypogonadal loss. Two different paradigms of steroid replacement following orchidectomy (ORX) were used as either preventative or therapeutic therapy. ORX was performed in male wild-type (WT), AR2.3-tg and AR3.6-tg mice at 5 months with immediate DHT replacement (prevention, higher turnover) or at 3 months with DHT treatment delayed for 2 months (therapeutic, lower turnover), both with treatment for the last 6 weeks. Dual energy x-ray absorptiometry (DXA), microcomputed tomography (μCT), and histomorphometry were performed. In the prevention model, ORX significantly reduced BMD and BMC in all genotypes compared to sham and DHT was effective at prevention of osteopenia. In the therapeutic model, all genotypes became osteopenic compared to sham, but after a prolonged hypogonadal period, delayed DHT treatment provided little benefit. μCT analysis of mid-shaft total bone in all genotypes generally showed reductions after ORX. Delayed DHT was ineffective at restoring bone volume in any genotype whereas immediate treatment prevented loss only in AR transgenic mice. Cortical thickness also decreased with ORX but immediate DHT treatment was effective to increase thickness only in WT mice, likely due to expansion of marrow volume in both AR-tg lines. In metabolically highly active cancellous bone, ORX resulted in lower bone volume/tissue volume (BV/TV) in all genotypes, consistent among 3 sites measured. Again with delayed treatment, there was little effect of DHT to restore BV/TV, but when administered at the time of ORX, DHT completely prevented the decrease in cancellous bone in all genotypes. Improvement in cancellous bone architecture was seen with immediate DHT replacement that was enhanced in AR transgenic lines compared to WT. In contrast, there were only modest changes in all genotypes using the delayed treatment paradigm. With ORX in both paradigms, trabecular number was decreased while spacing increased. Thus, androgen therapy is effective for the prevention of endosteal and cancellous osteopenia primarily through its anti-resorptive properties, but shows little anabolic action as a therapeutic strategy to restore bone. Given the similarity in response to androgen treatment in both AR transgenic lines, overlapping expression profiles suggest that the target cells mediating androgen action in vivo are mature osteoblast/osteocytes. Combined, these results demonstrate that in the adult mouse, androgen treatment can reduce bone resorption but has little overall anabolic activity.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Androgen prevents hypogonadal bone loss via inhibition of resorption mediated by mature osteoblasts/osteocytes

Wiren

Zhang

Olson

et al. 2012

Bone

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“…Once HT is no longer required for menopausal symptoms, it should generally be stopped. If ongoing bone protection is indicated, bisphosphonates 22 and other agents 23 have been shown to be highly effective cross-over therapies and prevent the often rapid bone loss which occurs on stopping HT. Finally, although the IMS 21 suggests that lower doses of HT (as well as, presumably, types and formulations different to CEE) may further reduce risks and sideeffects, they agree that the prospective evidence regarding fracture risk and CVD is still lacking.…”

Section: B Ht Not Indicatedmentioning

confidence: 99%

Hormone therapy in postmenopausal osteoporosis: 2008

Ascott-Evans

Sonnendecker

Villiers

2008

Journal of Endocrinology, Metabolism and Diabetes of South Afri

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“…Therefore, prolonged HRT for osteoporosis treatment is not recommended. In addition to this, reduction of bone density occurs more rapidly if HRT is stopped compared to normal reduction of bone density in menopausal women suffering from osteoporosis 20. Thus, due to the several adverse effects of HRT, women prefer to have nonhormonal treatments to manage their postmenopausal osteoporosis 21…”

Section: Introductionmentioning

confidence: 99%

Lactobacillus helveticus (ATCC 27558) upregulates Runx2 and Bmp2 and modulates bone mineral density in ovariectomy-induced bone loss rats

Parvaneh¹,

Karimi²,

Jamaluddin³

et al. 2018

CIA

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PurposeOsteoporosis is one of the major health concerns among the elderly population, especially in postmenopausal women. Many menopausal women over 50 years of age lose their bone density and suffer bone fractures. In addition, many mortality and morbidity cases among the elderly are related to hip fracture. This study aims to investigate the effect of Lactobacillus helveticus (L. helveticus) on bone health status among ovariectomized (OVX) bone loss-induced rats.MethodsThe rats were either OVX or sham OVX (sham), then were randomly assigned into three groups, G1: sham, G2: OVX and G3: OVX+L. helveticus (1 mL of 108–109 colony forming units). The supplementation was force-fed to the rats once a day for 16 weeks while control groups were force-fed with demineralized water.ResultsL. helveticus upregulated the expression of Runx2 and Bmp2, increased serum osteocalcin, bone volume/total volume and trabecular thickness, and decreased serum C-terminal telopeptide and total porosity percentage. It also altered bone microstructure, as a result increasing bone mineral density and bone strength.ConclusionOur results indicate that L. helveticus attenuates bone remodeling and consequently improves bone health in OVX rats by increasing bone formation along with bone resorption reduction. This study suggests a potential therapeutic effect of L. helveticus (ATCC 27558) on postmenopausal osteoporosis.

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Skeletal Consequences of Hormone Therapy Discontinuance: A Systematic Review

Cited by 17 publications

References 35 publications

Androgen prevents hypogonadal bone loss via inhibition of resorption mediated by mature osteoblasts/osteocytes

Androgen prevents hypogonadal bone loss via inhibition of resorption mediated by mature osteoblasts/osteocytes

Hormone therapy in postmenopausal osteoporosis: 2008

<em>Lactobacillus helveticus</em> (ATCC 27558) upregulates <em>Runx2</em> and <em>Bmp2</em> and modulates bone mineral density in ovariectomy-induced bone loss rats

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