Postmenopausal Osteoporosis (PMO)

Also known as: Osteoporosis, Postmenopausal / Postmenopausal Osteoporosis / Osteoporosis, Post-Menopausal / Post-Menopausal Osteoporosis / Osteoporosis Postmenopausal / Post Menopausal Osteoporosis / Postmenopausal Osteoporoses / Type I osteoporosis

DrugDrug NameDrug Description
DB06401BazedoxifeneBazedoxifene is a third generation selective estrogen receptor modulator (SERM), developed by Pfizer following the completion of their takeover of Wyeth Pharmaceuticals. In late 2013, Pfizer received approval for bazedoxifene as part of the combination drug DUAVEE in the prevention (not treatment) of postmenopausal osteoporosis. It is approved in the European Union (marketed in Italy and Spain) and Japan, and is in the late phases of review by the United States' Food and Drug Administration (FDA). Bazedoxifene is yet to be approved by the FDA.
DB00783EstradiolEstradiol (also known as E2 or 17β-estradiol) is a naturally occurring hormone that circulates endogenously within the human body. It is the most potent form of mammalian estrogenic steroids and acts as the major female sex hormone. As such, estradiol plays an essential role in the regulation of the menstrual cycle, in the development of puberty and secondary female sex characteristics, as well as in ageing and several hormonally-mediated disease states. Estrogen mediates its effects across the body through potent agonism of the Estrogen Receptor (ER), which is located in various tissues including in the breasts, uterus, ovaries, skin, prostate, bone, fat, and brain. Estradiol binds to both subtypes of the Estrogen Receptor: Estrogen Receptor Alpha (ERα) and Estrogen Receptor Beta (ERβ). Estradiol also acts as a potent agonist of G Protein-coupled Estrogen Receptor (GPER), which has recently been recognized as a major mediator of estradiol's rapid cellular effects [A31620]. Estradiol is commercially available in several hormone therapy products for managing conditions associated with reduced estrogen production such as menopausal and peri-menopausal symptoms as well as hypoestrogenism. It is also used in transgender hormone therapy, as a component of oral contraceptive pills for preventing pregnancy (most commonly as [DB00977], a synthetic form of estradiol), and is sometimes used for the palliative treatment of some hormone-sensitive cancers like breast and prostate cancer. Estradiol is available in a number of formulations including oral, transdermal, and injectable. The primary source of estrogen in normally cycling adult women is the ovarian follicle, which secretes 70 to 500 mcg of estradiol daily, depending on the phase of the menstrual cycle. However, after menopause, most endogenous estrogen is produced by conversion of androstenedione, secreted by the adrenal cortex, to estrone by peripheral tissues. Thus, estrone and the sulphate conjugated form, estrone sulphate, are the most abundant circulating estrogens in postmenopausal women [FDA Label]. Although circulating estrogens exist in a dynamic equilibrium of metabolic interconversions, estradiol is the principal intracellular human estrogen and is substantially more potent than its metabolites, estrone and estriol at the receptor level. Because of the difference in potency between estradiol and estrone, menopause (and a change in primary hormone from estradiol to estrone) is associated with a number of symptoms associated with this reduction in potency and in estrogenic effects. These include hot flashes, vaginal dryness, mood changes, irregular menses, chills, and sleeping problems. When used for oral or IM administration, estradiol is commonly synthesized as a pro-drug ester (such as [DB13952], [DB13953], [DB13954], [DB13955], and [DB13956]). It is commonly produced with an ester side-chain as endogenous estradiol has very low oral bioavailability on its own (2-10%). First-pass metabolism by the gut and the liver quickly degrades the estradiol molecule before it gets a chance to enter the systemic circulation and exert its estrogenic effects [A12102]. Esterification of estradiol aims to improve absorption after oral administration (such as with Estradiol valerate) or to sustain release from intramuscular depot injections (such as with Estradiol Cypionate) through improved lipophilicity [T84]. Following absorption, the esters are cleaved, resulting in the release of endogenous estradiol, or 17β-estradiol. Recommendations for treatment of menopausal symptoms changed drastically following the release of results and early termination of the Women's Health Initiative (WHI) studies in 2002 as a number of concerns were raised regarding the use of estrogen [A31626]. Specifically, the combined estrogen–progestin arm was discontinued after approximately five years of follow up due to a statistically significant increase in invasive breast cancer and in cardiovascular events [A31627]. Following extensive critique of the WHI results in the years following its release, Hormone Replacement Therapy (HRT) is now recommended to be used only for a short period (for 3-5 years post-menopause) in low doses, and in women without a history of breast cancer or at increased risk of cardiovascular or thromboembolic disease [A31628]. Notably, use of estrogen for menopausal symptoms should always be accompanied by a progestin component due to estrogen's effects on the endometrium; in women with an intact uterus, unopposed estrogen has been shown to promote the growth of the endometrium which can lead to endometrial hyperplasia and possibly cancer in the long-term. [DB00977] (EE) is a synthetic form of estradiol commonly used as the estrogenic component of most combination Oral Contraceptive Pills (OCPs). Ethinyl Estradiol differs from Estradiol in that it has improved biovailability and greater resistance to metabolism, making it more suitable for oral administration.
DB04574Estrone sulfateEstrone sulfate (as estropipate) is a form of estrogen. It has several uses such as: alleviate symptoms of menopause as hormone replacement therapy, treatment some types of infertility, treatment of some conditions leading to underdevelopment of female sexual characteristics, treatment of vaginal atrophy, treatment of some types of breast cancer (particularly in men and postmenopausal women), treatment of prostate cancer and prevention of osteoporosis.
DB00977EthinylestradiolA semisynthetic alkylated estradiol with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally and is often used as the estrogenic component in oral contraceptives. Ethinyl estradiol is marketed mostly as a combination oral contraceptive under several brand names such as Alesse, Tri-Cyclen, Triphasil, and Yasmin. The FDA label includes a black box warning that states that combination oral contraceptives should not be used in women over 35 years old who smoke due to the increased risk of serious cardiovascular side effects.
DB00367LevonorgestrelA synthetic progestational hormone with actions similar to those of progesterone and about twice as potent as its racemic or (+-)-isomer (norgestrel). It is used for contraception, control of menstrual disorders, and treatment of endometriosis. It is usually supplied in a racemic mixture (Norgestrel, 6533-00-2). Only the levonorgestrel isomer is active. Levonorgestrel is marketed mostly as a combination oral contraceptive under several brand names such as Alesse, Triphasil, and Min-Ovral.
DB00603Medroxyprogesterone acetateMedroxyprogesterone acetate (INN, USAN, BAN), also known as 17α-hydroxy-6α-methylprogesterone acetate, and commonly abbreviated as MPA, is a steroidal progestin, a synthetic variant of the human hormone progesterone. It is used as a contraceptive, in hormone replacement therapy and for the treatment of endometriosis as well as several other indications. MPA is a more potent derivative of its parent compound medroxyprogesterone (MP). While medroxyprogesterone is sometimes used as a synonym for medroxyprogesterone acetate, what is normally being administered is MPA and not MP.
DB00717NorethisteroneNorethisterone (INN, BAN), also known as Norethindrone (USAN), is a synthetic progestational hormone with actions similar to those of progesterone but functioning as a more potent inhibitor of ovulation. It has weak estrogenic and androgenic properties. The hormone has been used in treating amenorrhea, functional uterine bleeding, endometriosis, and for contraception.
DB00957NorgestimateNorgestimate is a form of progesterone, which is a female hormone important for the regulation of ovulation and menstruation. Norgestimate is used with estradiol to treat the symptoms of menopause.
DB00481RaloxifeneRaloxifene is a second generation selective estrogen receptor modulator (SERM) that mediates anti-estrogenic effects on breast and uterine tissues, and estrogenic effects on bone, lipid metabolism, and blood coagulation.[A4979,T28] Exhibiting tissue-specific effects distinct from [estradiol], raloxifene is the first of the benzothiophene group of antiestrogens to be labelled a SERM.[A4977] Available in many countries worldwide, raloxifene was initially approved by the FDA in December, 1997 under the market name Evista® for the management and prevention of osteoporosis in postmenopausal women and reduction in risk for invasive breast cancer in postmenopausal women with osteoporosis or those who are at high risk for invasive breast cancer. However, it has a negligible effect on altering the development and progression of breast cancer itself.[label] The most common causes of osteoporosis include postmenopausal deficiency of estrogen and age-related deterioration in bone homeostasis. Due to the risk of bone fractures that may lead to morbidities and reduced quality of life, the management of osteoporosis in postmenopausal women with the use of therapeutic agents in addition to concurrent therapies is critical. Due to the decline in estrogen levels in postmenopausal osteoporosis, hormone replacement therapy (HRT), such as estradiol, has been used to ameliorate the condition. However, due to the off-target actions by HRT, newer non-hormonal agents such as raloxifene and [tamoxifen] have been developed to reduce adverse events through selective pharmacological actions on tissue-specific therapeutic targets.[T28] The main effects of raloxifene are to preserve the bone mineral density and decrease the risk of breast cancer in postmenopausal women. Compared to estrogen and tamoxifen, raloxifene was not associated with an increased risk of uterine cancer and it does not cause endometrial proliferation.[A716] Although rare, there was an increased risk of venous thromboembolism during clinical trials of postmenopausal women receiving raloxifene. In addition, a clinical study consisting of postmenopausal women with documented coronary heart disease or at increased risk for coronary events showed an increased risk for fatal stroke with raloxifene therapy compared to placebo.[label] It is strongly advised that the risk-benefit ratio is considered before starting raloxifene therapy in women at risk of thromboembolic disease or strokes, such as the prior history of stroke, transient ischemic attack, atrial fibrillation, hypertension, or cigarette smoking.[label]
DrugDrug NameTargetType
DB06401BazedoxifeneEstrogen receptor alphatarget
DB06401BazedoxifeneUDP-glucuronosyltransferase 1A1enzyme
DB06401BazedoxifeneEstrogen receptor betatarget
DB06401BazedoxifeneUDP-glucuronosyltransferase 1-8enzyme
DB06401BazedoxifeneUDP-glucuronosyltransferase 1-10enzyme
DB00783EstradiolEstrogen receptor alphatarget
DB00783EstradiolNuclear receptor subfamily 1 group I member 2target
DB00783EstradiolSex hormone-binding globulincarrier
DB00783EstradiolEstrogen receptor betatarget
DB00783EstradiolCytochrome P450 1A2enzyme
DB00783EstradiolUDP-glucuronosyltransferase 1-1enzyme
DB00783EstradiolSerum albumincarrier
DB00783EstradiolFatty acid-binding protein, intestinalcarrier
DB00783EstradiolCytochrome P450 3A4enzyme
DB00783EstradiolCytochrome P450 3A5enzyme
DB00783EstradiolCytochrome P450 3A7enzyme
DB00783EstradiolSolute carrier family 22 member 2transporter
DB00783EstradiolSolute carrier family 22 member 1transporter
DB00783EstradiolSolute carrier family 22 member 3transporter
DB00783EstradiolSolute carrier organic anion transporter family member 2B1transporter
DB00783EstradiolSolute carrier organic anion transporter family member 1A2transporter
DB00783EstradiolMultidrug resistance-associated protein 7transporter
DB00783EstradiolSolute carrier family 22 member 11transporter
DB00783EstradiolATP-binding cassette sub-family G member 2transporter
DB00783EstradiolSolute carrier organic anion transporter family member 1B1transporter
DB00783EstradiolMultidrug resistance protein 1transporter
DB00783EstradiolCytochrome P450 1A1enzyme
DB00783EstradiolCytochrome P450 1B1enzyme
DB00783EstradiolCytochrome P450 2C19enzyme
DB00783EstradiolCytochrome P450 2C8enzyme
DB00783EstradiolCytochrome P450 2C9enzyme
DB00783EstradiolSolute carrier family 22 member 8transporter
DB00783EstradiolSolute carrier organic anion transporter family member 1B3transporter
DB00783EstradiolSolute carrier organic anion transporter family member 1C1transporter
DB00783EstradiolSolute carrier organic anion transporter family member 4A1transporter
DB00783EstradiolNeuronal acetylcholine receptor subunit alpha-4target
DB00783EstradiolNuclear receptor coactivator 2target
DB00783EstradiolG-protein coupled estrogen receptor 1target
DB00783EstradiolATP synthase subunit atarget
DB00783EstradiolEstradiol 17-beta-dehydrogenase 2target
DB00783EstradiolEstrogen-related receptor gammatarget
DB04574Estrone sulfateCytochrome P450 1A2enzyme
DB04574Estrone sulfateCytochrome P450 3A4enzyme
DB04574Estrone sulfateEstrogen receptor alphatarget
DB04574Estrone sulfateEstrogen receptor betatarget
DB04574Estrone sulfateSex hormone-binding globulincarrier
DB04574Estrone sulfateSerum albumincarrier
DB04574Estrone sulfateCytochrome P450 2C9enzyme
DB04574Estrone sulfateMultidrug and toxin extrusion protein 1transporter
DB04574Estrone sulfateMultidrug and toxin extrusion protein 2transporter
DB00977EthinylestradiolEstrogen receptor alphatarget
DB00977EthinylestradiolNuclear receptor subfamily 1 group I member 2target
DB00977EthinylestradiolCytochrome P450 3A4enzyme
DB00977EthinylestradiolCytochrome P450 2C8enzyme
DB00977EthinylestradiolBile salt export pumptransporter
DB00977EthinylestradiolSodium/bile acid cotransportertransporter
DB00977EthinylestradiolCanalicular multispecific organic anion transporter 1transporter
DB00977EthinylestradiolMultidrug resistance protein 1transporter
DB00977EthinylestradiolSex hormone-binding globulintarget
DB00977EthinylestradiolUDP-glucuronosyltransferase 1-1enzyme
DB00367LevonorgestrelProgesterone receptortarget
DB00367LevonorgestrelEstrogen receptor alphatarget
DB00367Levonorgestrel3-oxo-5-alpha-steroid 4-dehydrogenase 1target
DB00367LevonorgestrelCytochrome P450 3A4enzyme
DB00367LevonorgestrelCytochrome P450 19A1enzyme
DB00367LevonorgestrelAndrogen receptortarget
DB00367LevonorgestrelSex hormone-binding globulintarget
DB00603Medroxyprogesterone acetateProgesterone receptortarget
DB00603Medroxyprogesterone acetateEstrogen receptor alphatarget
DB00603Medroxyprogesterone acetateCytochrome P450 3A4enzyme
DB00603Medroxyprogesterone acetateCytochrome P450 2C8enzyme
DB00603Medroxyprogesterone acetate3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2enzyme
DB00603Medroxyprogesterone acetateCytochrome P450 2C9enzyme
DB00717NorethisteroneProgesterone receptortarget
DB00717NorethisteroneCytochrome P450 3A4enzyme
DB00717NorethisteroneMultidrug resistance protein 1transporter
DB00717NorethisteroneCytochrome P450 2C19enzyme
DB00717NorethisteroneCytochrome P450 3A5enzyme
DB00717NorethisteroneCytochrome P450 3A7enzyme
DB00717NorethisteroneSerum albumincarrier
DB00717NorethisteroneSex hormone-binding globulincarrier
DB00957NorgestimateProgesterone receptortarget
DB00957NorgestimateEstrogen receptor alphatarget
DB00957NorgestimateCanalicular multispecific organic anion transporter 1transporter
DB00957NorgestimateCytochrome P450 3A4enzyme
DB00957NorgestimateAndrogen receptortarget
DB00481RaloxifeneEstrogen receptor alphatarget
DB00481RaloxifeneEstrogen receptor betatarget
DB00481RaloxifeneAldehyde oxidaseenzyme
DB00481RaloxifeneCytochrome P450 2C8enzyme
DB00481RaloxifeneCytochrome P450 2B6enzyme
DB00481RaloxifeneCytochrome P450 19A1enzyme
DB00481RaloxifeneCytochrome P450 3A4enzyme
DB00481RaloxifeneSerpin B9target
DB00481RaloxifeneTrefoil factor 1target
DB00481RaloxifeneUDP-glucuronosyltransferase 1-1enzyme
DB00481RaloxifeneSerum albumincarrier
DB00481RaloxifeneAlpha-1-acid glycoprotein 1carrier
DB00481RaloxifeneSolute carrier organic anion transporter family member 1B1transporter
DB00481RaloxifeneSolute carrier organic anion transporter family member 1B3transporter
DB00481RaloxifeneMultidrug resistance protein 1transporter
DB00481RaloxifeneATP-binding cassette sub-family G member 2transporter
DB00481RaloxifeneCanalicular multispecific organic anion transporter 1transporter
DB00481RaloxifeneCanalicular multispecific organic anion transporter 2transporter
DB00481RaloxifeneMultidrug resistance-associated protein 4transporter
DB00481RaloxifeneUDP-glucuronosyltransferase 1-10enzyme
DB00481RaloxifeneUDP-glucuronosyltransferase 1-8enzyme
DrugDrug NamePhaseStatusCount
DB06548Minodronic acid1Completed1
DB05829Parathyroid hormone1Completed1
DB00017Salmon Calcitonin1Completed1
DB06285Teriparatide1 / 2Active Not Recruiting1
DB00630Alendronic acid2Completed4
DB06724Calcium Carbonate2Completed1
DB13975Cimicifuga racemosa2Completed1
DB05829Parathyroid hormone2Completed1
DB00884Risedronic acid2Completed2
DB00399Zoledronic acid2Completed1
DB12148Menatetrenone2 / 3Recruiting1
DB01022Phylloquinone2 / 3Recruiting1
DB00630Alendronic acid3Completed3
DB00630Alendronic acid3Withdrawn1
DB00720Clodronic acid3Completed1
DB00884Risedronic acid3Completed7
DB00017Salmon Calcitonin3Completed3
DB00399Zoledronic acid3Completed2
DB00945Acetylsalicylic acid4Recruiting1
DB00630Alendronic acid4Completed4
DB00630Alendronic acid4Recruiting1
DB06643Denosumab4Active Not Recruiting1
DB00710Ibandronate4No Longer Available1
DB09125Potassium Citrate4Unknown Status1
DB00884Risedronic acid4Completed8
DB00884Risedronic acid4Terminated1
DB09267Strontium ranelate4Completed2
DB06285Teriparatide4Active Not Recruiting1
DB11094Vitamin D4Completed3
DB00399Zoledronic acid4Active Not Recruiting1
DB00399Zoledronic acid4Completed3
DB00399Zoledronic acid4Not Yet Recruiting1
DB00399Zoledronic acid4Recruiting1
DB00630Alendronic acidNot AvailableActive Not Recruiting1
DB00630Alendronic acidNot AvailableCompleted1
DB00630Alendronic acidNot AvailableNot Yet Recruiting1
DB06401BazedoxifeneNot AvailableActive Not Recruiting1
DB06643DenosumabNot AvailableCompleted3
DB01395DrospirenoneNot AvailableCompleted1
DB00783EstradiolNot AvailableCompleted1
DB00710IbandronateNot AvailableCompleted1
DB00481RaloxifeneNot AvailableActive Not Recruiting1
DB06285TeriparatideNot AvailableActive Not Recruiting1
DB06285TeriparatideNot AvailableCompleted2
DB00399Zoledronic acidNot AvailableCompleted2