You are in: eMedicine Specialties > Physical Medicine and Rehabilitation > MEDICAL DISEASES Osteoporosis (Secondary)Article Last Updated: Aug 11, 2006AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Alana C Serota, MD, Fellow in Metabolic Bone Disease and Osteoporosis, Department of Orthopedics, Hospital for Special Surgery Alana C Serota is a member of the following medical societies: American Academy of Family Physicians and North American Menopause Society Coauthor(s): Joseph M Lane, MD, Professor of Orthopedic Surgery, Weill Medical College of Cornell University; Chief, Metabolic Bone Disease Service, Hospital for Special Surgery; William S Whyte II, MD, Director of Interventional Spine and Pain Management, Louisiana Pain Physicians; Curtis W Slipman, MD, Director, University of Pennsylvania Spine Center, Associate Professor, Department of Physical Medicine and Rehabilitation, University of Pennsylvania Medical Center; David Lenrow, MD, Vice Chair of Clinical Services, Medical Director, Erdman Clinic; Associate Professor, Department of Rehabilitation Medicine, University of Pennsylvania at Philadelphia Editors: Elizabeth A Moberg-Wolff, MD, Associate Professor, Department of Physical Medicine and Rehabilitation, Medical College of Wisconsin; Consulting Staff, Department of Physical Medicine and Rehabilitation, Children's Hospital of Wisconsin; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Michael T Andary, MD, MS, Residency Program Director, Associate Professor, Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine; Kelly L Allen, MD, Consulting Staff, Department of Physical Medicine and Rehabilitation, Lourdes Regional Rehabilitation Center, Our Lady of Lourdes Medical Center; Denise I Campagnolo, MD, MS, Director of Multiple Sclerosis Clinical Research and Staff Physiatrist, Barrow Neurology Clinics, St. Joseph's Hospital and Medical Center; Investigator for Barrow Neurology Clinics; Director, NARCOMS Project for Consortium of MS Centers, Phoenix Author and Editor Disclosure Synonyms and related keywords: metabolic bone disease, fracture, vertebral compression fracture, hip fracture, secondary osteoporosis, bone mineral density, BMD INTRODUCTIONSection 2 of 10
  BackgroundOsteoporosis, a chronic progressive disease, is the most common metabolic bone disease in the United States. Osteoporosis can affect almost the entire skeleton. Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility. The disease often does not become clinically apparent until a fracture occurs. Consequently, many individuals, both male and female, experience pain, disability, and diminished quality of life as a result of having osteoporosis. The economic burden of the disease in the United States is considerable and will grow as the population ages. Prevention and recognition of the secondary causes of osteoporosis are first-line measures to lessen the impact of osteoporosis. A Gallup survey performed by the National Osteoporosis Foundation revealed that 75% of all women aged 45-75 years have never discussed osteoporosis with their physicians; however, treatment to prevent future fractures is available. Bone mineral density (BMD) in a patient is related to peak bone mass and, subsequently, bone loss. The World Health Organization has established the following definitions of osteoporosis based on bone mass density measurements in white women:
Patients within this group who have already experienced 1 or more fractures are deemed to have severe or established osteoporosis. Although these definitions are necessary to establish the prevalence of osteoporosis, they should not be used as the sole determinant of treatment decisions. PathophysiologyUnderstanding the pathogenesis of osteoporosis starts with knowing how bone formation and remodeling occur. Osteoblasts are osteoid formers, and osteoclasts are bone resorbers. Both osteoblasts and osteoclasts are formed in the bone marrow. Bone formation is not static; it is a system that is remodeled constantly. In adults, approximately 25% of trabecular bone is resorbed and replaced every year, compared with only 3% of cortical bone. Bone is continually remodeled throughout life because bones sustain recurring microtrauma. Bone remodeling occurs at discrete sites within the skeleton and proceeds in an orderly fashion. Bone resorption is always followed by bone formation, a phenomenon referred to as coupling. In osteoporosis, this coupling mechanism is thought to be unable to keep up with the constant microtrauma to trabecular bone. The hallmark of osteoporosis is a reduction in skeletal mass caused by an imbalance between bone resorption and bone formation. Loss of gonadal function and aging are the 2 most important factors contributing to the development of this condition. Studies have shown that bone loss in women accelerates rapidly in the first years after menopause. The lack of gonadal hormones is thought to up-regulate osteoclast progenitor cells. In contrast to postmenopausal bone loss, which is associated with excessive osteoclast activity, the bone loss that accompanies aging is associated with a progressive decline in the supply of osteoblasts in proportion to the demand. This demand is ultimately determined by the frequency with which new multicellular units are created and new cycles of remodeling are initiated. Osteoporosis may be confused with osteomalacia. The normal human skeleton is composed of a mineral component, calcium hydroxyapatite (60%), and organic material, mainly collagen (40%). In osteoporosis, the bones are porous and brittle, while in osteomalacia the bones are soft. This difference in bone consistency is related to the proportion of mineral to organic material content. In osteoporosis, the mineral-to-collagen ratio is within the reference range, whereas in osteomalacia, the proportion of mineral composition is reduced relative to organic mineral content. Biomechanics An understanding of the biomechanics of bone provides greater appreciation as to why bone may be susceptible to an increased risk of fracture. When vertical loads are placed on bone, such as tibial and femoral metaphyses and vertebral bodies, a substantial amount of bony strength is derived from the horizontal trabecular cross-bracing system. This system of horizontal cross-bracing trabeculae assists in supporting the vertical elements, thus limiting lateral bowing and fractures that may occur with vertical loading. Disruption of such trabecular connections is known to occur preferentially in patients with osteoporosis, particularly in postmenopausal women, making females more at risk than males for vertebral compression fractures. In 1998, Rosen and Tenenhouse studied the unsupported trabeculae and their susceptibility to fracture within each vertebral body. They found an extraordinarily high prevalence of trabecular fracture callus sites within vertebral bodies examined at autopsy, typically 200-450 healing or healed fractures per vertebral body. These horizontal trabecular fractures are asymptomatic, and their accumulation reflects the impact of lost trabecular bone and greatly weakens the cancellous structure of the vertebral body. The reason for preferential osteoclastic severance of horizontal trabeculae is unknown. Some authors have attributed this phenomenon to overaggressive osteoclastic resorption. FrequencyUnited StatesMost studies assessing the prevalence and incidence of osteoporosis use the rate of fracture as a marker for the presence of this disorder, although BMD also relates to risk of disease and fracture. The risk of new vertebral fractures increases by a factor of 2-2.4 for each SD decrease of bone density measurement. In 1998, statistics from the National Osteoporosis Foundation estimated that more than 10 million men and women in the United States have osteoporosis and nearly 19 million more have low bone mass, placing them at increased risk for osteoporosis and fractures. Women and men with metabolic disorders associated with secondary osteoporosis have a 2- to 3-fold higher risk of hip and vertebral fractures. InternationalOsteoporosis is a very common metabolic bone disease worldwide, with similar incidence as noted in the United States. Mortality/MorbidityMany individuals experience morbidity associated with the pain, disability, and diminished quality of life caused by osteoporosis-related fractures. Hip fractures are known to increase mortality rates in both men and women. Secondary complications of hip fractures include nosocomial infections and pulmonary thromboembolism. While the overall prevalence of hip fracture is greater in women than in men, a similar number of men and women die as a consequence of hip fractures because men with hip fractures have a higher mortality rate. The impact of vertebral fractures increases and they increase in number. As posture worsens and kyphosis progresses, patients experience difficulty with balance, back pain, respiratory compromise, and an increased risk of pneumonia. Overall function declines, and patients may lose their ability to live independently. RaceIn 1981, Melton et al reported that the prevalence of hip fractures is higher in white populations, regardless of geographic location. Another study indicated that the incidence of hip fractures was lower among African Americans in the United States and South Africa compared to age-matched white populations within the same continent. More recently, a study of Japanese American women in Hawaii found a 5% incidence of vertebral fractures each year among individuals aged 80 years. SexWomen have a 2-fold increase in the number of fractures resulting from nontraumatic causes, compared with men of the same age. Men have a higher prevalence of secondary osteoporosis, with an estimated 45-60% being a consequence of hypogonadism, alcoholism, or glucocorticoid excess. Only 35-40% of osteoporosis diagnosed in men is considered primary in nature. AgeIn 1982, Jensen et al studied Danish women aged 70 years and found a 21% prevalence of vertebral fractures. In 1989, Melton et al reported that 27% of women in their study had evidence of vertebral fractures by age 65 years. The number of osteoporotic fractures increases with age. Wrist fractures typically occur first, when individuals are aged approximately 50-59 years. Vertebral fractures occur more often in the seventh decade of life, and hip fractures occur more often in the eighth decade of life (see the information bullet on secondary osteoporosis, under Causes.). CLINICALSection 3 of 10
History
PhysicalThe physical examination should begin with an inspection of the patient. Height measurement with a stadiometer at each visit is useful.
CausesOsteoporosis has been divided into several classifications according to etiology and localization in the skeleton. Osteoporosis is initially divided into localized and generalized categories. These 2 main categories are classified further into primary and secondary osteoporosis.
DIFFERENTIALSSection 4 of 10
|
| SPA | DPA | DXA | QCT Scanning | |
|---|---|---|---|---|
| Time | 5-15 min | 20-30 min | 5-10 min | 10-30 min |
| Cost | $50-150 | $150-300 | $100-200 | $150-300 |
| Sites Scanned | Radius, forearm, calcaneus | Spine, hip (anteroposterior) | Spine (lateral), hip, radius | Spine (lateral), hip, radius |
Osteoblasts are derived from mesenchymal stem cells, whereas osteoclasts are derived from hematopoietic precursors. The 2 types of cells are dependent on each other for production. In fact, the development of osteoclasts from hematopoietic precursors cannot be accomplished unless mesenchymal cells are present. Mesenchymal cells with the potential to become osteoblasts also have the potential to become fibroblasts, chondrocytes, adipocytes, or muscle cells. This potential for differentiation allows the osteoblast to secrete the same cytokines and colony-stimulating factors produced by fibroblasts.
Hematopoietic granulocyte-macrophage colony-forming units (CFUs) produce osteoclasts and give rise to monocytes and macrophages. As such, the osteoclasts produce the same cytokines that monocytes produce. Interleukin (IL)–6 is produced, in part, by osteoblasts that stimulate osteoclastic activity. This phenomenon is one proposed mechanism for certain diseases that exhibit increased bone resorption. Two examples of diseases that result in osteoporosis by this mechanism are multiple myeloma and rheumatoid arthritis.
Jilka et al have demonstrated that IL-6 regulates osteoclasts, and the scientific community gained insight into the role played by cytokines in the development of osteoporosis. Jilka et al studied mice. They either removed the ovaries from the mice, or they performed sham operations. IL-6 levels and the number of granulocyte-macrophage CFUs were measured. IL-6 and granulocyte-macrophage CFU levels were much higher in the ovariectomized mice. This finding provided evidence that estrogen inhibits the secretion of IL-6, and IL-6 contributes to the recruitment of osteoclasts from the monocyte cell line, thus contributing to osteoporosis. IL-1 has also been shown to be involved in the production of osteoclasts.
The production of IL-1 is increased in bone marrow mononuclear cells from ovariectomized rats. Administering IL-1 receptor antagonist to these animals prevents the late stages of bone loss induced by the loss of ovarian function, but it does not prevent the early stages of bone loss. The increase in the IL-1 in the bone marrow does not appear to be a triggered event, but is a result of removal of the inhibitory effect of sex steroids on IL-6 and other genes directly regulated by sex steroids.
The first goal of rehabilitation in osteoporosis patients is to control pain if a fracture has occurred. Physical therapy then focuses on improving function and reducing disability. Spinal compression fractures can be extremely painful and can cause short- and long-term morbidity. Oral analgesics on a regular schedule can be implemented. Pain-relieving modalities such as moist hot packs and transcutaneous electrical nerve stimulation should also be considered. During this period of acute pain management, monitoring the patient carefully for signs of constipation, urinary retention, and respiratory depression, which can occur with the use of narcotic analgesics, is essential.
A comfortable mechanical support for the spine and, in some cases, a thoracic orthosis, may need to be prescribed. The primary reason for the application of a thoracic orthosis is to limit motion in the spine. The length of time a patient should wear a rigid spinal orthosis is undetermined. What is well known is that immobilization contributes to bone demineralization.
During the early mobilization period, deep breathing exercises, pectoral and intercostal strengthening, and back conservation techniques need to be implemented.
As soon as the course of therapy allows, weightbearing exercises should be initiated. Weightbearing activities are essential for maintenance of bone mass (Wolff law). Aerobic low-impact exercises, such as walking and bicycling, generally are recommended. During these activities, ensure the patient maintains an upright spinal alignment. In 1984, Sinaki and Mikkelsen showed that exercises that place flexion forces on the vertebrae tend to cause an increase in the number of vertebral fractures in patients.
Although swimming is not a weightbearing exercise that will improve BMD, it does provide chest expansion, spinal extension, and low-impact cardiopulmonary fitness.
Isometric exercises should be used to strengthen abdominal muscles, aiding in the prevention of a kyphosis.
Home modification focuses on reducing the risk of falling by installing handrails and grab bars in hallways, stairs, and bathrooms. The use of a shower chair, tub bench, and adaptive bathing devices also can be beneficial. The application of nonskid tape to steps (indoors and outdoors), as well as the removal of throw rugs, greatly improves home safety.
Percutaneous vertebroplasty (PVP) with polymethylmethacrylate (PMMA) was developed in 1984. The first indication for this treatment was aggressive vertebral angiomas. PVP with PMMA was then used for other lesions that weakened the vertebral body, such as malignant tumors. PMMA is the principal component of bone cements used for rapid stable fixation of implants, such as metal and plastic prosthetics placed in living bone during orthopedic procedures. PVP is one therapeutic alternative for the treatment of pain associated with compression fractures. PMMA is used in PVP to fortify a collapsed vertebral body and stabilize the vertebral column. Success with vertebroplasty is limited by the lack of significant height restoration and the high rate of cement extravasation.
The second therapeutic alternative for vertebral compression fractures is balloon kyphoplasty, whereby the vertebra is initially expanded with an inflatable balloon tamp. This reduces the fracture and restores height to the vertebral body. The balloon is then removed and cement is injected into the cavity under lower pressure than that used in PVP, thereby reducing the risk of cement extravasation.
PVP and balloon kyphoplasty are indicated in patients with incapacitating and persistent severe focal back pain related to vertebral collapse. At the primary author's institution, vertebroplasty is used for lesions above T8 and kyphoplasty is used for the remainder.
In 1997, Jensen et al studied age-related or steroid-induced osteoporotic vertebrae with partial compression fractures in patients who underwent PVP with PMMA. A total of 48 vertebrae in 30 patients were injected, and 90% of the patients described marked improvement of pain within 1 week of treatment. All the patients who experienced pain relief noted increased mobility and decreased need for narcotics. The patients were tracked for an average of 9 months, and the rate of long-term pain relief was reported to be approximately 80%. Whether this pain relief was related to mechanical stabilization of the spine or was secondary to neurotoxic effects of PMMA remains to be determined.
Traditional operative management of vertebral compression fractures is uncommon and is usually reserved for gross spinal deformity or for threatened or existing neurologic impairment. Operative interventions include anterior and posterior decompression and stabilization with placement of such internal fixation devices as screws, plates, cages, or rods. Bone grafting is routinely performed to achieve bony union. The failure rate of spinal arthrodesis is significant because achieving adequate fixation of hardware in osteoporotic bone is difficult. Moreover, patients who are elderly have a reduced osteogenic potential.
Consultation with a nonsurgical spine specialist is appropriate for a patient who is not a surgical candidate or whose symptoms persist despite surgical fixation. Consultation with a spine surgeon is appropriate for patients with intractable, severe, function-limiting symptomatology that has not been relieved by noninterventional techniques.
Currently, no treatment can completely reverse established osteoporosis. Early intervention can prevent osteoporosis in most people. For patients with established osteoporosis, medical intervention can halt its progression. If secondary osteoporosis is present, treatment for the primary disorder should be provided.
Prevention of osteoporosis has 2 components, behavior modification and pharmacologic interventions. In 1998, the National Osteoporosis Foundation outlined that the following factors should be modified to reduce the risk of development of osteoporosis: cigarette smoking; physical inactivity; and intake of alcohol, caffeine, sodium, animal protein, and calcium. The pharmacologic prevention methods include calcium supplementation and administration of estrogen, raloxifene, and bisphosphonates (with the exception of intravenous ibandronate).
Some of the preventative measures are also used in the treatment of osteoporosis. The goal of the current recommendations for daily calcium intake is to ensure that individuals maintain an adequate calcium balance. Several large studies have demonstrated that supplementation of calcium and vitamin D resulted in a 30-70% reduction of fracture rates over 2-4 years.
In 1994, the National Institutes of Health recommended the following daily calcium intake:
Vitamin D is increasingly being recognized as a key element in overall bone health and muscle function. The minimum daily requirement in patients with osteoporosis is 800 IU of vitamin D3, or cholecalciferol. Many patients require more, continuously or for a short period, to be considered vitamin D replete, defined as a serum 25-hydroxyvitamin D level of 32 ng/mL.
Although not currently recommended for the treatment of osteoporosis, HRT is important to mention because many osteoporosis patients in a typical practice still use it for controlling postmenopausal symptoms. The results of the Women's Health Initiative were distressing with respect to the adverse outcomes associated with combined estrogen and progesterone therapy (eg, risks for myocardial infarction, stroke, deep venous thrombosis, and breast cancer) and estrogen alone (eg, risks for stroke and deep venous thrombosis); however, it was the first randomized controlled trial that demonstrated that HRT was efficacious in preventing nonvertebral fractures, in the order of 35%.
US Food and Drug Administration–approved pharmacologic treatment options for osteoporosis include raloxifene, calcitonin, bisphosphonates, and teriparatide (human recombinant PTH 1-34).
Raloxifene is part of a class of compounds termed selective estrogen receptor modulators (SERMs), which provide the beneficial effects of estrogen without the potentially adverse outcomes. Raloxifene has been shown to prevent bone loss, and data in females with osteoporosis have demonstrated that raloxifene causes a 35% reduction in the risk of vertebral fractures. It has also been shown to reduce the prevalence of invasive breast cancer. Raloxifene has been shown to increase the incidence of deep vein thrombosis and hot flashes. In 601 postmenopausal women who had daily therapy with raloxifene, BMD was increased, serum concentrations of total low-density lipoprotein cholesterol were lowered, and the endometrium was not stimulated.
Calcitonin is a hormone that decreases osteoclast activity, thereby impeding postmenopausal bone loss. Results from a single controlled clinical trial indicate that calcitonin may decrease osteoporotic vertebral fractures by approximately 30%. In the first 2 years, calcitonin has been found to increase spinal BMD by approximately 2%. Calcitonin also has an analgesic property that makes it ideally suited for the treatment of acute vertebral fractures. Calcitonin is delivered as a single daily intranasal spray that provides 200 U of the drug. The drug can be delivered subcutaneously, but this route is rarely used.
Bisphosphonates have been used for the prevention and treatment of osteoporosis. When used for prevention, the recommended dose of both alendronate and risedronate is 5 mg/d. In a study by Hosking et al, doses of 2.5 mg and 5 mg of alendronate were evaluated in postmenopausal women who did not have osteoporosis. They found that the women who received placebo lost BMD at all measured sites, whereas the women treated with 5 mg/d of alendronate had a mean increase in BMD of 3.5% ± 0.2% at the lumbar spine, 1.9% ± 0.1% at the hip, and 0.7% ± 0.1% for the total body (all, P <.001).
Alendronate has been shown to increase both spinal and hip mineral density in postmenopausal women. Well-conducted controlled clinical trials using alendronate sodium indicate that treatment reduces the rate of fracture at the spine, hip, and wrist by 50% in patients with osteoporosis. The treatment dose of alendronate is 70 mg/wk, to be taken sitting upright with a large glass of water at least 30 minutes before eating in the morning. Newer bisphosphonates include risedronate, dosed at 35 mg every weekend, and ibandronate, dosed at 150 mg/mo. The latter has not shown efficacy in nonvertebral fractures in the clinical trials. Ibandronate is also available as an intravenous formulation that is given every 3 months. It is an excellent choice for patients intolerant to oral bisphosphonates or in those in whom adherence is an
issue.
Over time, bisphosphonate therapy decreases bone turnover and, at very high levels in animals, decreases bone strength and resilience. Some limited reports, including that by Odvina et al from 2005, describe patients on long-term bisphosphonate therapy developing transverse stress fractures; biopsy specimens of these individuals have suggested extremely low turnover states. Therefore, while the bisphosphonates are outstanding in their efficacy, bone turnover markers should be monitored; if these become profoundly suppressed, the patient should be taken off the bisphosphonates and given a rest period until he or she can return to therapeutic levels (NTx, 20-40).
Teriparatide, human recombinant PTH 1-34, is the only available anabolic agent for the treatment of osteoporosis. When PTH is given continuously, it is associated with increased osteoclastic and osteoblastic turnover, leading to a net loss of bone. However, in an intermittent subcutaneous administration of 20 mcg/d, PTH has been demonstrated to lead to a very active anabolic phase, with bone mass increasing up to 13% over 2 years in the spine and to a lesser degree within the hip (Dempster, 2001; Neer, 2001; Body, 2002).
Most studies with PTH have been performed on women. The medication decreases the risk of vertebral and nonvertebral fractures to the same extent as bisphosphonates. Teriparatide is given for a maximum of 2 years, after which time the gains in BMD achieved with PTH are secure and can even be augmented with bisphosphonate therapy, otherwise the BMD slowly deteriorates to pretreatment levels (Kurland, 2004).
According to Finkelstein et al in 2003, initial studies using a combination of concurrent PTH and bisphosphonate therapy showed decreased benefit compared with therapy with either agent alone; therefore, the general recommendation is that these drugs be given separately and in sequence. A 2005 study by Cosman and colleagues challenged this conclusion by giving 3-month-on, 3-month-off pulses of teriparatide while the subjects were on weekly alendronate; BMD in the spine increased above that of the alendronate-only arm. This pulsed regimen appears to take advantage of the 3- to 4-month so-called anabolic window, in which the markers of bone formation rise more quickly than the markers of bone resorption.
Studies by Deal et al from 2005 and Ste-Marie et al from 2006 on women have shown that the concurrent use of estrogen or raloxifene can enhance the bone-forming effects of teriparatide. Data on the use of PTH in men are much more limited, but they appear to have relatively comparable efficacy.
Indications for PTH in men and women are a bone density decline while on bisphosphonate therapy, bone density stabilization while on extremely low-level bisphosphonate therapy, a fracture occurring while on bisphosphonate therapy, or a very low initial bone turnover rate for which an anabolic effect is clearly warranted.
Denosumab is a novel agent that has been studied in both cancer patients and in patients with postmenopausal osteoporosis. It is a fully human monoclonal antibody against RANKL (ie, receptor activator of nuclear factor kappa-B ligand). RANKL is a key mediator of the resorptive phase of bone remodeling. In patients with multiple myeloma or bone metastases from breast cancer, a single subcutaneous dose of denosumab decreases bone turnover markers within 1 day, and this effect is sustained through 84 days at the higher doses used in one study. Although no fracture data are available as yet, denosumab was shown to increase BMD and decrease bone resorption in postmenopausal women with osteoporosis over a 12-month period.
Denosumab is currently in phase 3 clinical studies for both metastatic bone disease and postmenopausal osteoporosis. Because the overactivity of RANKL is a major factor in bone loss in patients with autoimmune and inflammatory disorders such as ulcerative colitis, denosumab may become first-line therapy for these patients.
Restore effects of decreased steroid hormone levels. Estrogens may be administered orally or by transdermal (skin) patch (eg, estradiol [Vivelle, Climara, Estraderm, Esclim, Alora]).
| Drug Name | Conjugated estrogens/medroxyprogesterone acetate (Prempro) |
|---|---|
| Description | Estrogens reduce bone resorption and retard or halt postmenopausal bone loss. |
| Adult Dose | 0.625 mg/2.5 mg or 0.625 mg/5 mg tab PO qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; undiagnosed vaginal bleeding; thrombophlebitis; liver disease |
| Interactions | May decrease hypoprothrombinemic effects of anticoagulants; rifampin may decrease serum concentrations; aminoglutethimide may increase hepatic metabolism of medroxyprogesterone |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Estrogens and progestins may cause fluid retention; acute intermittent porphyria may be precipitated by estrogens |
| Drug Name | Ethinyl estradiol and norethindrone (FemHRT) |
|---|---|
| Description | Used to treat moderate-to-severe vasomotor symptoms and to prevent osteoporosis associated with menopause. |
| Adult Dose | 1 tab PO qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; endometrial and hepatic cancer; thromboembolic disorders; undiagnosed vaginal bleeding; persons >35 y who smoke; cardiovascular disease |
| Interactions | Phenobarbital, phenytoin, paramethadione, carbamazepine, troglitazone, rifampicin, and griseofulvin induce enzymes that decrease levels of contraceptive steroids; oral anticoagulants may increase thromboembolic potential |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Caution in patients diagnosed with hepatic impairment, migraines, seizure disorders, cerebrovascular disorders, breast cancer, or thromboembolic disease |
Affect some of the receptors stimulated by estrogen but can selectively act as antagonist or agonist, depending on the organ system.
| Drug Name | Raloxifene (Evista) |
|---|---|
| Description | SERM that decreases bone loss. |
| Adult Dose | 60 mg PO qd |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; active thromboembolic disorder |
| Interactions | None reported |
| Pregnancy | X - Contraindicated in pregnancy |
| Precautions | Caution in history of venous thromboembolism, pulmonary embolism, cardiovascular disease, renal or hepatic insufficiency, and cervical/uterine carcinoma; caution in persons concurrently taking estrogens |
Inhibit osteoclastic bone resorption
| Drug Name | Calcitonin (Miacalcin nasal spray) |
|---|---|
| Description | Directly inhibits osteoclastic bone resorption and decreases tubular resorption of calcium, phosphate sodium, magnesium, and potassium. |
| Adult Dose | 200 U (1 puff)/d intranasally |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Have epinephrine immediately available for possible anaphylactic reaction |
Analogs of pyrophosphate. Act by binding to hydroxyapatite in bone matrix, thereby inhibiting the dissolution of crystals. Prevent osteoclast attachment to the bone matrix, osteoclast recruitment, and viability.
| Drug Name | Alendronate (Fosamax) |
|---|---|
| Description | Inhibits bone resorption via actions on osteoclasts or osteoclast precursors. |
| Adult Dose | 70 mg PO qwk |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; hypocalcemia; esophageal abnormalities; inability to stand upright for 30 min |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Must be taken at least 30 min before first food, beverage, or medication of the day and should be taken with large amounts of water; caution in renal impairment |
| Drug Name | Ibandronate (Boniva) |
|---|---|
| Description | Inhibits osteoclast-mediated bone resorption. In postmenopausal women, reduces bone turnover rate, leading to a net gain in bone mass. |
| Adult Dose | 2.5 mg PO qd; administer with water at least 1 h prior to first food or beverages (other than water) of the day Alternatively, 150 mg PO once monthly on the same date each month or 3 mg IV push (infuse over 15-30 seconds) q3mo |
| Pediatric Dose | Not established |
| Contraindications | Documented hypersensitivity; uncorrected hypocalcemia; inability to stand or sit upright for at least 60 min following drug administration |
| Interactions | Multivalent cations (eg, calcium, aluminum, magnesium, iron) decrease absorption (administer at least 1 h prior to vitamin and mineral supplements); NSAIDs may aggravate GI irritation |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | May cause upper GI disorders (eg, dysphagia, esophagitis, ulceration); minimize GI risk by standing or sitting upright 1 h following dose; calcium and vitamin D supplementation required; not recommended with severe renal impairment (ie, CrCl <30 mL/min) |
| Drug Name | Risedronate (Actonel) |
|---|---|
| Description | Potent aminobisphosphonate. Inhibits bone resorption via actions on osteoclasts or osteoclast precursors. Has been shown to reduce bone resorption and increase BMD of spine by 5% and femoral neck by 1.6%. Also has been shown to reduce incidence of vertebral fracture by 41% and nonvertebral fracture by 39% over a period of 3 y in postmenopausal women. |
| Adult Dose | Prevention or treatment: 5 mg PO qd; alternatively, 35 mg PO qwk |
| Pediatric Dose | Not established |
| Contraindications | Patients with hypocalcemia, documented hypersensitivity to any component of the product; inability to remain upright for 30 min; not recommended for use in patients with severe renal impairment (CrCl <30 mL/min) |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor hypercalcemia-related parameters (eg, serum levels of calcium, phosphate, magnesium, potassium); maintain adequate intake of calcium and vitamin D to prevent severe hypocalcemia; caution if active upper GI problems; do not administer with alendronate for osteoporosis in postmenopausal women; adverse effects include diarrhea, headache, and arthralgia |
Promote new bone formation, leading to increased BMD. Teriparatide is a biological product containing a portion of human PTH, which primarily regulates calcium and phosphate metabolism in bones. Teriparatide is approved for men or women at high risk of fracture due to primary or hypogonadal osteoporosis or postmenopausal osteoporosis, respectively.
| Drug Name | Teriparatide (Forteo) |
|---|---|
| Description | Recombinant human PTH 1-34, which has identical sequence to 34 N-terminal amino acids (biologically active region) of 84-amino acid human PTH. Acts as endogenous PTH, thus regulating calcium and phosphate metabolism in bone and kidneys. Works primarily to stimulate new bone by increasing number and activity of osteoblasts (bone-forming cells). Additional physiological actions include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption. When administered with calcium and vitamin D, teriparatide increases BMD and decreases risk of fractures in patients with osteoporosis. |
| Adult Dose | 20 mcg SC qd |
| Pediatric Dose | Not for use in children |
| Contraindications | Documented hypersensitivity; increased risk for osteosarcoma (including those with Paget disease of bone or unexplained elevations of alkaline phosphatase, open epiphyses, or prior radiation therapy involving the skeleton); children or growing adults; patients with bone metastases or history of skeletal malignancies and those with metabolic bone diseases other than osteoporosis |
| Interactions | None reported |
| Pregnancy | C - Safety for use during pregnancy has not been established. |
| Precautions | Monitor for hypercalcemia; may cause orthostatic hypotension (particularly following first several doses), dizziness, or leg cramps |