what does treatment with bisphosphonate (bp) do?

Bisphosphonates

are a group of drugs that work by slowing bone loss. They reduce the risk of hip and spine fractures. Bone renewal is a slow process, but in many people an increase in bone density can be measured over five years of treatment. Uses Bisphosphonates can be used to reduce the risk of hip and spine fractures in osteoporosis.

Full Answer

What are bisphosphonates (BP)?

Bisphosphonates are a group of drugs that work by slowing bone loss. They reduce the risk of hip and spine fractures. Bone renewal is a slow process, but in many people an increase in bone density can be measured over five years of treatment. Uses Bisphosphonates can be used to reduce the risk of hip and spine fractures in osteoporosis.

Can bisphosphonates be given intravenously?

Bisphosphonates help prevent your bones from losing calcium and other minerals by slowing or stopping the natural processes that dissolve bone tissue. In doing this, they help your bones remain strong and intact.

When are bisphosphonates indicated in the treatment of renal insufficiency?

During the past 2 decades, bisphosphonate therapy has become the leading clinical intervention for postmenopausal osteoporosis because of the ability of bisphosphonates to selectively suppress osteoclast activity and thereby retard bone resorption.

Why are bisphosphonates used to treat osteoporosis?

 · Bisphosphonates are used in the prevention and treatment of postmenopausal osteoporosis and some are approved for the treatment of osteoporosis in men. They can help prevent fractures of the spine, hip, and wrist in people with osteoporosis and prevent bone loss for men and women taking steroids. Bisphosphonates work by slowing cells that break down …

How does bisphosphonate therapy work?

Bisphosphonates work by slowing down the cells which break down bone (osteoclasts). Therefore they slow down bone loss, allowing the bone building cells (osteoblasts) to work more effectively. They can help to strengthen bone and help to prevent it getting any weaker.

What happens to blood calcium levels when taking bisphosphonates?

Bisphosphonates decrease bone resorption by inhibiting osteoclastic activity. This is accompanied by an increase in calcium balance and in the mineral content of bone. The consequent increase in bone mass is the basis by which these compounds prevent osteoporosis in man.

What is the benefit of bisphosphonates?

Bisphosphonates lower fracture risk in large part by reducing the rate of bone remodeling and associated microarchitectural deterioration of bone as well as by increasing bone mass.

How do bisphosphonates work in osteogenesis imperfecta?

Osteogenesis imperfecta is caused by a genetic defect resulting in an abnormal type I collagen bone matrix which typically results in multiple fractures with little or no trauma. Bisphosphonates are used in an attempt to increase bone mineral density and reduce these fractures in people with osteogenesis imperfecta.

Why do bisphosphonates lower calcium?

By inhibiting bone resorption, bisphosphonates reduce calcium efflux from bone into the circulation, leading to the development of hypocalcemia.

How do bisphosphonates treat hypercalcemia?

Bisphosphonates inhibit osteoclastic bone resorption and are effective in the treatment of hypercalcemia due to conditions causing increased bone resorption and malignancy-related hypercalcemia. Pamidronate and etidronate can be given intravenously, while risedronate and alendronate may be effective as oral therapy.

What is the most common side effect of bisphosphonate?

Upset Stomach/Esophageal Inflammation The most common side effect of bisphosphonate medications is stomach upset. The medication can cause inflammation of the esophagus and even lead to erosions of the surface of the esophagus.

When are bisphosphonates indicated?

They are indicated for the treatment and prevention of osteoporosis. In post-menopausal females with osteoporosis who have already sustained a low-trauma fracture, treatment with bisphosphonates reduces the relative risk of an additional fracture by between 30–70% over three to five years compared with placebo.

How long should you be on bisphosphonates?

Bisphosphonates, the most common type of osteoporosis medications, are typically taken for at least 3 to 5 years. After that, your doctor will consider your risk factors in determining whether you should continue to take these or other osteoporosis medications.

What is the current treatment for osteogenesis imperfecta?

To date, there is no known treatment, medicine, or surgery that will cure osteogenesis imperfecta (OI). The goal of treatment is to prevent deformities and fractures and allow the child to function as independently as possible. Treatments for preventing or correcting symptoms may include: Care of fractures.

What medications help with osteogenesis imperfecta?

Bisphosphonates are the only drugs specifically licensed for the treatment of osteogenesis imperfecta (OI). The most commonly used drug in this class is pamidronate.

Is osteogenesis imperfecta autosomal dominant?

When caused by mutations in the COL1A1 or COL1A2 gene, osteogenesis imperfecta has an autosomal dominant pattern of inheritance, which means one copy of the altered gene in each cell is sufficient to cause the condition.

What are bisphosphonates used for?

What are bisphosphonates and why are they used in lupus treatment? Bisphosponates such as risedronate (Actonel), alendronate (Fosamax), ibandronate (Boniva), zoledronic acid (Reclast), and pamidronate (Aredia) are used to treat and prevent osteoporosis—or, bone thinning—which occurs when the bones lose calcium and other minerals ...

How do bisphosphonates help with osteoporosis?

In people with osteoporosis, the bones lose minerals faster than they can be regenerated. Bisphosphonates help prevent your bones from losing calcium and other minerals by slowing or stopping the natural processes that dissolve bone tissue. In doing this, they help your bones remain strong and intact. If you have already developed osteoporosis, these medications may slow the thinning of your bones and help prevent bone fractures (broken bones). In fact, studies have shown that alendronate (Fosamax) and risedronate (Actonel) can lower your risk of fractured vertebrae—bone segments that make up your spine—by 50%. Similar studies demonstrate that these medications can lower the chance of breaking other bones by 30-49%.

Can you take ibuprofen for Lupus?

Certain medications can affect how your body deals with bisphosphonates. Your lupus treatment may involve several medications, but you should still tell your doctor if you are taking any other medicines—prescription drugs, over-the-counter medications, supplements, and vitamins—especially NSAIDs, such as ibuprofen (Advil, Motrin), celecoxib (Celebrex), naproxen (Aleve, Naprosyn), meloxicam (Mobic), and diclofenac (Voltaren, Cataflam). In addition, antacids and other supplements that contain aluminum, calcium, and magnesium can interfere with how your body absorbs bisphosphonates, so you should not take these medicines for at least 30 minutes after taking your bisphosphonate tablet.

What is the most common clinical condition for which bisphosphonate therapy is used?

The most common clinical condition for which bisphosphonate therapy is used is osteoporosis, a skeletal condition characterized by compromised bone strength resulting in an increased risk of fracture. As previously noted, osteoporosis is a clinically heterogeneous disease with a range of origins, including hormone loss (postmenopausal and androgen-deprivation), iatrogenic (glucocorticoid-induced and transplant-related), physical (immobility), and genetic (eg, juvenile and OI-associated). Often these conditions overlap within individual patients.

What are bisphosphonates used for?

Since their introduction to clinical practice more than 3 decades ago, bisphosphonates have been increasingly used for an array of skeletal disorders . Bisphosphonates are now used to treat such varied conditions as heritable skeletal disorders in children, postmenopausal and glucocorticoid-induced osteoporosis (GIO), and bone metastases in patients with malignancies. Bisphosphonates can offer substantial clinical benefit in conditions in which an imbalance between osteoblast-mediated bone formation and osteoclast-mediated bone resorption underlies disease pathology; however, the more recently recognized association of bisphosphonate use with pathologic conditions, including low bone turnover states with resultant pathologic fractures, osteonecrosis of the jaw (ONJ), and an increased incidence of atrial fibrillation, has brought increased scrutiny to the current broad use of bisphosphonate therapy.

What is the primary therapy for osteoclasts?

As aforementioned, bisphosphonates promote the apoptosis of osteoclasts actively engaged in the degradation of mineral on the bone surface. Accordingly, bisphosphonates have become the primary therapy for managing skeletal conditions characterized by increased osteoclast-mediated bone resorption. Such excessive resorption underlies several pathologic conditions for which bisphosphonates are now commonly used, including multiple forms of osteoporosis (juvenile, postmenopausal or involutional [senile], glucocorticoid-induced, transplant-induced, immobility-induced, and androgen-deprivation–related), Paget disease of bone, osteogenesis imperfecta (OI), hypercalcemia, and malignancy metastatic to bone.

How long after taking bisphosphonate can you eat?

A previous impediment for many patients prescribed oral bisphosphonate therapy was the inconvenience associated with daily oral administration (requiring patients to remain upright for 30 minutes and refrain from eating any food both 2 hours before and at least 30 minutes after pill ingestion) and the relatively common association with gastrointestinal symptoms. The more recent development of pharmacologically equivalent preparations allowing for once-weekly (alendronate or risedronate) or even monthly (ibandronate or risedronate) oral administration has profoundly affected bisphosphonate delivery for most patients for whom convenience (and thus adherence to therapy) was an issue and has correspondingly lead to higher rates of adherence.17,18Further, the availability of IV preparations (pamidronate, ibandronate, and zoledronic acid), which for most clinical conditions require even less frequent dosing, has eliminated the gastrointestinal adverse effects incurred by some patients managed with oral bisphosphonates, although the rate of acute phase reactions characterized by flulike symptoms (low-grade fever, myalgias and arthralgias, or headache) is increased in patients receiving IV rather than oral bisphosphonate treatment.14

How long does bisphosphonate suppress bone resorption?

As might be anticipated, length of suppression is largely a function of bisphosphonate potency for mineral matrix binding, such that the most potent bisphosphonate, zoledronic acid, at a dose of either 4 mg13or 5 mg (the dose approved by the Food and Drug Administration [FDA] for osteoporosis),14effectively suppresses biochemical markers of bone resorption for up to 1 year in women with postmenopausal osteoporosis. Although the precise biologic half-lives of the currently used nitrogen-containing bisphosphonates remain the subject of debate largely because of technical challenges required to determine bisphosphonate levels in urine and serum, estimates for the potent bisphosphonate alendronate suggest a biologic half-life of more than 10 years after single-dose IV administration.15

Does bisphosphonate cause osteoclast apoptosis?

Although bisphosphonate-mediated induction of osteoclast apoptosis cannot be measured directly within the clinical setting , a temporal reduction in biochemical markers of bone resorption (namely amino- and carboxyl-terminal breakdown products of type 1 collagen in serum and urine) after bisphosphonate initiation is considered a reasonably reliable surrogate of bisphosphonate efficacy and potency. Maximum suppression of bone resorption occurs within approximately 3 months of initiation of oral bisphosphonate therapy given daily, weekly, or monthly and remains roughly constant with continuation of treatment.10–12Resorption is suppressed more rapidly after intravenous (IV) bisphosphonate administration than after oral bisphosphonate therapy.

What are the nitrogen-containing bisphosphonates?

The mechanism by which nitrogen-containing bisphosphonates promote osteoclast apoptosis is distinct from that of the non–nitrogen-containing bisphosphonates. As elegantly illustrated in recent studies, nitrogen-containing bisphosphonates bind to and inhibit the activity of farnesyl pyrophosphate synthase, a key regulatory enzyme in the mevalonic acid pathway critical to the production of cholesterol, other sterols, and isoprenoid lipids6,7(Figure 2, A). As such, the posttranslational modification (isoprenylation) of proteins (including the small guanosine triphosphate–binding proteins Rab, Rac, and Rho, which play central roles in the regulation of core osteoclast cellular activities including stress fiber assembly, membrane ruffling, and survival) is inhibited,8ultimately leading to osteoclast apoptosis.9Interestingly, whereas farnesyl pyrophosphate synthase is ubiquitously expressed in mammalian cells and has a critical role in lipid production, cellular apoptosis induced by nitrogen-containing bisphosphonates appears to occur only in osteoclasts. This is likely a direct function of the ability of bisphosphonates to selectively adhere to and be retained within bone before endocytosis within osteoclasts during osteoclast-mediated bone mineral dissolution and matrix digestion (Figure 2, B). Given the fact that nearly all patients now receive treatment with the more potent nitrogen-containing bisphosphonates rather than the earlier non–nitrogen-containing bisphosphonates, the remainder of this review focuses on this more recent class of bisphosphonates.

How do bisphosphonates work?

We know that bisphosphonates can: interfere with the formation of osteoclasts. make osteoclasts self destruct or die early. change the signalling between osteoclasts and osteoblasts. form a barrier between the bone and the osteoclast.

What is the role of bisphosphonate in bone breakdown?

The osteoclast cells, which break down old bone, absorb the bisphosphonate drug. Their activity is slowed down. This reduces bone breakdown.

How do bisphosphonates affect osteoclasts?

We know that bisphosphonates can: 1 interfere with the formation of osteoclasts 2 make osteoclasts self destruct or die early 3 change the signalling between osteoclasts and osteoblasts 4 form a barrier between the bone and the osteoclast

Why is stopping bone cancer important?

help to prevent complications from other cancers that have spread to the bones. Cancer cells seem to be attracted to an environment where bones are being broken down. Researchers hope that stopping this process could slow cancer growth and help people live longer, as well as reduce bone damage.

What are the side effects of bisphosphonates?

Two more serious adverse events, atypical subtrochanteric fractures and osteonecrosis of the jaw, have been associated with bisphosphonates. Read more about these two side effects.

What is BP in biology?

Bisphosphonates (BP) are synthetic compounds with a common phosphorus-carbon-phosphorus bond and have a high affinity for the calcium hydroxyapatite of the bone. Among them, the nitrogenous BPs are potent inhibitors of bone resorption as they inhibit the farnesyl diphosphate synthase (FPPS) osteoclast enzyme in the mevalonate pathway causing its activity to decrease. A decrease of bone formation is then observed secondarily [1] Roelofs, A.J., et al., Molecular mechanisms of action of bisphosphonates: current status. Clin Cancer Res, 2006. 12 (20 Pt 2): p. 6222s-6230s.

Does alendronate increase BMD?

In the long-term (5-6 years), alendronate and zoledronic acid have been shown to continuously increase BMD at the lumbar spine, but not at the hip where BMD reaches a plateau. Patients at high risk of fractures, particularly vertebral fractures, are the ones who will benefit of continued treatment [10] Black, D.M., et al., The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res, 2012. 27 (2): p. 243-54.

Does zoledronic acid help with osteopenia?

Zoledronic acid has been shown to reduce the risk of nonvertebral and vertebral fragility fractures, not only in women with osteoporosis, but also in women with osteopenia [9] Reid, I.R., et al., Fracture Prevention with Zoledronate in Older Women with Osteopenia. N Engl J Med, 2018. 379 (25): p. 2407-2416.

Does alendronate reduce hip fracture risk?

Reductions in non-vertebral fracture risk (20-30%) and hip fracture risk (40-50%) have also been demonstrated for alendronate, risedronate and zoledronic acid, but not for ibandronate [3] Black, D.M., et al., Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group. Lancet, 1996. 348 (9041): p. 1535-41.

Is bisphosphate a complication of osteoporosis?

Osteoporosis is a common complication of acute fracture, which can lead to fracture delayed union or other complications and resulting in poor fracture healing. Bisphosphate is a common anti-osteoporosis drug, but its application in fracture patients is still controversial because of its inhibitory effect on bone resorption.

Does bisphosphate increase bone resorption?

A total of 16 studies involving 5022 patients obtained from selected databases were examined. As expected, bisphosphate had no significant effect on fracture healing time, but it could significantly increase BMD and prevent osteoporosis. Meanwhile, bisphosphate can inhibit both bone resorption and bone formation markers, resulting in low bone turnover state.

Does bisphosphonate affect bone synthesis?

This meta-analysis showed that bisphosphonate have no significant effect on frac ture healing time but they do increase the changes in BMD and reduce bone synthesis and resorption markers. Early application of bisphosphonates after injury in the appropriate patient population should be considered.

Does bisphosphonate help with fractures?

For fracture patients, the use of BPs can significantly reduce the recurrence rate of fractures (10). However, the role of BPs in fragility fracture healing is not well elucidated with study results ranging from improved healing, no effect, and inhibition of healing (4, 11–17). Earlier studies have shown that the incidence of low impact hip fractures and the rate of recurrent fractures is significantly increased after more than 5 years of long-term bisphosphonate treatment. However, some patients in the above studies are not simply osteoporotic patients. For instance, patient may also have Paget’s disease, which could have influenced the clinical outcome. In animal studies, BPs have been shown to cause low bone turnover (18). Other studies have shown that bisphosphonate can promote fracture healing in vivoand in vitro(14, 19), accelerating the formation of trabecular bone and the thickness of cortical bone callus (20). There is a lack of sufficient data and human research on the effect of BPs on fracture healing.

When were bisphosphonates first used?

The widespread introduction of bisphosphonates into clinical practice, which occurred after Food and Drug Administration (FDA) approval of alendronate in 1995 , was largely driven by the use of this class of skeletal antiresorptive agents to treat postmenopausal osteoporosis. A wealth of information from well-designed clinical trials clearly shows that, as a class, bisphosphonates are highly effective at limiting the loss of bone mass, deterioration of bone microarchitecture, and increased fracture risk that occur with aging. Additional approved indications for bisphosphonates currently include other forms of osteoporosis (such as that which occurs in men or is associated with glucocorticoid therapy), Paget disease of bone, hypercalcemia of malignancy, and metastatic bone disease.

What are the side effects of bisphosphonate?

Some adverse effects that may occur with bisphosphonate therapy, such as gastroesophageal irritation, were recognized early on. Other more serious potential complications, including osteonecrosis of the jaw (ONJ) and severe suppression of bone turnover, have only more recently been appreciated and reflect the relative rarity of such adverse effects. This concise review addresses the short-term, long-term, common, and rare adverse effects associated with bisphosphonate therapy. Other important considerations associated with bisphosphonate therapy, including the importance of ensuring adequate calcium and vitamin D intake, the availability of the World Health Organization fracture risk assessment (FRAX) algorithm1for estimating absolute fracture risk, and uncertainty about the dose and duration, are also discussed.

Can CTX be used for ONJ?

Key point: Data do not support using serum CTX for ONJ risk assessment. In patients with substantially increased risk of fracture (due to previous fractures or on the basis of FRAX determination before beginning bisphosphonate therapy), physicians should ensure that alternative strategies for dental care have been discussed with the patient's dentist and that the patient understands the best estimate of risk of ONJ development. In patients at low risk of fracture (such as in primary prevention), stopping therapy for 3 months periprocedurally is unlikely to substantially alter fracture risk or lead to bone loss but may help patients' peace of mind. Patients should be aware that no evidence shows that such stoppage will limit ONJ risk, which is already low in nearly all patients except those receiving frequent IV dosing in oncologic treatment regimens.

What is CTX for bone resorption?

Recently, measurement of the bone resorption marker carboxy-terminal collagen crosslinks (CTX) has been recommended in the oral surgery literature as a method for estimating the risk of developing ONJ. In their report of 30 cases of ONJ associated with oral bisphosphonate use, Marx et al17suggested that serum CTX levels be used to stratify patients receiving bisphosphonate therapy as having low, moderate, or high risk of developing ONJ. Unfortunately, the described report did not include any control patients who were receiving bisphosphonates but did not have ONJ, nor were any indices of bone remodeling on any patient before bisphosphonate initiation available. Thus, although it is possible that serum CTX measurement may be a useful adjunct in considering how to manage a patient who presents with ONJ, available data do not support serum CTX testing for identification of patients who may be at increased risk of ONJ.18Further, discontinuation of bisphosphonate therapy in patients at increased risk of fracture until a serum CTX value reaches a predefined threshold value may lead to an increased risk of fracture.

Does bisphosphonate cause hypocalcemia?

Transient hypocalcemia with seconda ry hyperparathyroidism is a recognized but underappreciated consequence of bisphosphonate administration. Because of the limited absorptive potential of oral bisphosphonates, hypocalcemia occurs most frequently after IV infusion and appears to occur most often in patients with hypoparathyroidism, impaired renal function, hypovitaminosis D, limited calcium intake, or high rates of osteoclast-mediated bone resorption (such as Paget disease of bone or a large skeletal tumor burden). In a study that measured levels of serum calcium in patients with cancer complicated by bone metastases, total serum calcium levels declined an average of 2 mg/dL (to convert to mmol/L, multiply by 0.25) at 7 days and nearly 3 mg/dL at 21 days after infusion of 4 mg of zoledronic acid.12

Can bisphosphonates cause pain?

Key point: Rarely, bisphosphonates can cause severe musculoskeletal pain. In patients who present with such symptoms, consideration of temporary or permanent drug discontinuation should be considered.

Can bisphosphonate cause musculoskeletal pain?

Although all oral and IV bisphosphonate preparations list musculoskeletal pain as a potential adverse effect in their prescribing information, the FDA recently issued an alert highlighting the possibility of severe and sometimes incapacitating bone, joint, and/or musculoskeletal pain that may occur at any point after patients begin taking a bisphosphonate.11Although discontinuation of bisphosphonate therapy improves symptoms in some patients, others appear to have slow or incomplete resolution. Risk factors for and the incidence of this potential adverse effect of bisphosphonates are unknown.