Hormone replacement therapy (HRT)
Bisphosphonates (sold as Fosamax, Actonel, Didrocal)
Raloxifene (sold as Evista) – a selective (o)estrogen receptor modulator
Strontium ranelate (sold as Protos)
Tibolone (sold as Livial)
Parathyroid hormone (PTH)
Denosumab (sold in the US as Prolia and Xgeva)

Hormone replacement therapy

Hormone replacement therapy (HRT, also called just Hormone Therapy) at the time of menopause may be beneficial for protecting bones.

The Women's Health Initiative trial (WHI, published July 2002 and October 2003) showed that hormone therapy, using oestrogen and progestin, does reduce the incidence of fractures at the hip and vertebrae (spinal bones) in postmenopausal women.^36,37 However, long-term use of this type of hormone therapy is associated with other risks of heart disease, breast cancer, pulmonary embolism (blood clots in the lung) and deep vein thrombosis (blood clots in the leg veins).³⁶The WHI trial of oestrogen alone in women who have had a hysterectomy also showed a reduction in fracture risk, with no increase in heart disease or breast cancer, but a small increase in the risk of stroke in women aged 50 to 79 years.^92,93

Although HRT has beneficial effects on bone health, it should be prescribed primarily for the short-term treatment (for less than five years) of menopausal symptoms in women who are progressing through menopause.

The use of hormone therapy for disease prevention is not recommended. However, some women may elect to use hormone therapy in this way. This needs to be done in consultation with your treating physician, so that you understand the risks and benefits of this therapy.³⁸

It is also important to realise that HRT only protects your bones for the duration of the treatment. Once treatment is discontinued, the rate of bone loss will return to the level it was at before starting HRT.³⁹

For further information on HRT, visit our Managing Menopause website.

Bisphosphonates

Bisphosphonates are drugs of a specific class that function to decrease bone loss.

Currently available bisphosphonates in Australia
Brand Name	Generic Name
Fosamax	alendronate
Fosamax plus D	alendronate + cholecalciferol (vitamin D3)
Actonel	risedronate
Actonel Combi	risedronate +calcium carbonate
Actonel Combi D	risedronate +calcium carbonate & vitamin D
Didrocal	etidronate + calcium

Alendronate and risendronate

Both alendronate (sold as Fosamax) and risedronate (sold as Actonel) have been found to reduce the incidence of vertebral (spinal bones) and hip fractures.^40,41 These drugs also reduce the risk of fracture at other sites in the body. The effects of these drugs on risk of fracture usually start within six to twelve months of commencing therapy.

These medications are generally well tolerated. They have been associated with some side effects including heartburn, abdominal discomfort and ulceration of the oesophagus (food pipe). Ulceration of the oesophagus is one of the most concerning side effects. Hence, these medications must be taken first thing in the morning on an empty stomach, with a full glass of water, and the individual needs to remain either sitting upright or standing for the next 30 min. After this time, normal activities and eating can be resumed. The incidence of oesophageal ulceration is extremely low when these medications are taken correctly.

These medications can be taken either daily or once weekly. There is an increasing trend for prescribing these drugs once weekly, as it improves compliance and it is likely to further reduce the incidence of gastrointestinal upset.³⁸ It is advisable that these medications be used cautiously by people who suffer significant heartburn and/or have a hiatus hernia.

These drugs are not well absorbed, so it is important to take them on an empty stomach. It is also recommended not to take calcium at the same time as the bisphosphonate, as calcium may interfere with the absorption of the bisphosphonate.

Fosamax plus D provides the added benefit of a weekly dose (2,800 IU) vitamin D, equivalent to 400 IU per day. See also vitamin D.

Actonel combi is also a combination medicine, combining risedronate and calcium: Patients take a risedronate tablet once per week, and calcium carbonate tablets on the other six days of the week (1250 mg per day).

Actonel Combi D® comprises risedronate tablets (taken once per week) and sachets of calcium carbonate and vitamin D that are mixed with water and taken daily on the other six days of the week. See also calcium.

Didrocal

Didrocal (etidronate + calcium) is administered in a somewhat different way to the other medications. This preparation is administered ‘cyclically’: For a two week period the active tablet etidronate is taken twice daily. This is then followed by an eleven week period where a calcium tablet is taken once daily. This cycle is then repeated. Didrocal is generally well tolerated and does not cause side effects of the upper gastrointestinal system such as heartburn or oesophageal ulceration. There may be side effects of diarrhoea or nausea. Generally this treatment has been found to be effective in increasing bone mineral density and reducing the incidence of vertebral (spinal) fractures. This medication is probably best suited to women with osteoporosis of the spine.⁴²

Non oral forms of bisphosphonates

If women are unable to tolerate the oral forms of the bisphosphonates, there is the option to have forms of medication given intravenously in an intermittent fashion. In this setting it is necessary for women to be under the care of a specialised physician or osteoporosis clinic.

Considerations and Issues of Bisphosphonates

In order for bisphosphonates to be effective in increasing bone mineral density and reducing the likelihood of fracture, women need to ensure that they have an appropriate intake of calcium (through diet and/or supplements) and that they have adequate levels of vitamin D. Some preparations of bisphosphonates come with calcium and/or vitamin D supplements, but patients may need to take additional supplements if their levels are inadequate..

Bisphosphonates should be prescribed to individuals at high risk of fractures. Your doctor will normally consider your bone density, history of low trauma fracture and other risk factors for osteoporosis before deciding on treatment. The Australian government currently subsidises the cost of bisphosphonates through the Pharmaceutical Benefits System (PBS) for the following individuals:

• Patients who have sustained a low trauma fracture regardless of their bone density
• Individuals older than 70 years who have a T-score less than -3.0, regardless of whether they have sustained a fracture
• Individuals who are taking prednisolone doses greater than 7.5 mg per day for more than three months, and who also have a T-score of less than -1.0 (At present, only risedronate is available on the PBS for this indication)

There may be certain situations where individuals are at high risk of fracture but do not meet the PBS criteria. It is best to speak to your treating doctor in these situations.

Osteonecrosis of the jaw (ONJ)

Bisphosphonates have recently been linked to a rare potential side-effect named osteonecrosis of the jaw (ONJ). ONJ occurs when an area of exposed bone persists for more than six weeks after removal of a tooth. The risk appears to be very low, with an estimated incidence of one in 2,000-10,000.⁹⁵  The majority of cases have occurred when patients have been taking potent, high dose intravenous bisphosphonates for management of bone cancers. The risk of ONJ associated with taking oral bisphosphonates is extremely low. It is advisable to have a dental health check prior to commencing bisphosphonates. If you are already taking bisphosphonates, you should inform your dentist, particularly if you need to have a tooth removed.

It is highly recommended that you discuss any concerns you might have about bisphosphonate therapy with your treating doctor before deciding to stop treatment.

Atypical Fractures

There is a theoretical concern that long term bisphosphonate therapy may lead to increased brittleness of bone, which might predispose patients to unusual fractures. These fractures have been described occurring at the shaft of the thigh bones. At present it is not clear whether these atypical fractures are due to bisphosphonate therapy or the osteoporosis that is being treated. In any case, they are extremely rare and any decision to stop treatment with bisphosphonates should be discussed with your treating doctor.

Raloxifene (sold as Evista)

Raloxifene (sold as Evista) belongs to a class of drugs known as selective (o)estrogen-receptor modulators, or SERMs. These drugs act like the hormone oestrogen at some sites in the body, but as an anti-oestrogen at other sites. In bone, raloxifene works like oestrogen and leads to an increase in bone mass (density). In the breast and uterus, it works as an anti-oestrogen and therefore does not stimulate the breast or uterine lining. Due to its anti-oestrogen effects in the breast, raloxifene reduces the incidence of breast cancer.

Primarily, raloxifene has been shown to reduce the incidence of vertebral (spinal) fractures.⁴³ Evidence for this drug having a significant effect on fracture risk at other sites of the body is lacking.

The side effects of raloxifene include hot flushes. This therapy is therefore problematic for premenopausal women and women who are currently going through menopause, as it may worsen menopausal symptoms. This therapy is best reserved for postmenopausal women, i.e. those who have already gone through menopause.

Another side effect of raloxifene is a slightly increased risk of deep vein thrombosis (DVT): Women taking this medication should consider stopping treatment if they are going to be immobile for some time, such as during long airline flights or during hospital admission. Treatment can be resumed once mobility is regained. Any woman who has significant risk factors for a clotting disorder should not be prescribed raloxifene.

Strontium ranelate (sold as Protos)

Strontium ranelate (sold as Protos) is an approved medication for treatment of osteoporosis in postmenopausal women. It is taken in the form of granules mixed with water, and should be taken at bedtime at least two hours after eating.

Strontium is a trace element that is naturally found within soft tissues, blood, teeth and bone. Its mode of action is unclear, but it seems to reduce bone loss and may enhance bone formation. It also becomes incorporated into bone, and will therefore lead to an artificial elevation of bone density when measured by DXA.

Studies with strontium ranelate in postmenopausal women have shown a reduction in vertebral (spinal) fractures and, in a higher fracture risk group, evidence that hip fractures are also reduced..^48,49 Strontium ranelate also appears to be well tolerated, but may be associated with side effects such as diarrhoea.

Like other osteoporosis therapies, there may be a requirement for additional vitamin D and calcium supplements if measured vitamin D levels are low or dietary calcium intake is insufficient.

Tibolone (sold as Livial)

Tibolone (sold as Livial) is a form of hormone therapy for treating menopausal symptoms. Tibolone may not have the same stimulatory effects on the breast as standard forms of hormone therapy. However, this has yet to be evaluated in properly conducted clinical trials. There is evidence that tibolone has beneficial effects on bone, causing an increase in bone mineral density and reducing the risk of vertebral and non-vertebral fractures.⁴⁴  A slightly increased risk of stroke has been seen in patients taking tibolone, so women who are already at risk of stroke should not be treated with this drug.

Parathyroid Hormone (PTH)

Parathyroid hormone (PTH) is listed on the Australian Pharmaceutical Benefits System (PBS) for treatment of severe osteoporosis. It is mainly reserved for patients who have continued to suffer fractures despite specific osteoporosis treatment and who have very low bone mineral density. PTH is administered daily via a subcutaneous (just below the skin) injection and is not given concurrently with other specific osteoporosis treatments such as bisphosphonates. It functions to increase bone formation. In Australia, treatment is limited to one 18-month course per lifetime, due to an increased risk of bone cancer that was identified in animal testing. Patients who have a history of bone cancer or irradiation of their bones are not eligible for treatment. There appears to be a clear benefit in terms of reducing all types of fractures in postmenopausal women, except for hip fractures.^46,47 Due to the expense and limited accessibility of this therapy, its use is confined to specialists in osteoporosis.

Denosumab (sold in the US as Prolia and Xgeva)

Denosumab (sold in the US as Prolia and Xgeva) is a new medication for treatment of osteoporosis. It is a highly specific antibody that reduces the activity of the bone cells responsible for bone breakdown. This results in an increase in bone density and a reduction in fractures at all sites. The treatment is given as an injection under the skin and lasts for six months. The main side-effect is a slight increase in the risk of skin infections.

Content updated 29 July, 2011