Pharmacological treatments for postmenopausal women with osteoporosis are prescribed to decrease the risk of fragility fractures. Many drugs with different mechanisms of action have been approved for the prevention and treatment of osteoporosis, are effective and available worldwide. These medications must be used in conjunction with calcium and vitamin D supplements, recommended lifestyle changes, adequate nutrition and physical activity.

The commonly available treatments are:

• Bisphosphonates
• Menopausal hormone replacement therapy (MHT), also known as hormone replacement therapy (HRT), and Selective oestrogen Receptor Modulators (SERM)
• Denosumab
• Anabolics

Calcitonin, due to its limited anti-fracture efficacy relative to other available agents, is not considered a first-line therapy, it is no longer available in Europe and will not be discussed.

Strontium Ranelate is another agent with modest evidence of efficacy. Due to the restriction of use in Europe and its unavailability in the USA, this compound will not be discussed further.

Treatments can be divided into two categories: 

• Anti-resorptive agents, which include oestrogen, selective oestrogen receptor modulators (SERM), bisphosphonates (BP) and denosumab, reduce bone resorption (and subsequently bone formation), preserving bone mineral density (BMD).
• Anabolic agents, which include teriparatide (PTH1-34) and abaloparatide (34 amino acid synthetic analogue of parathyroid hormone-related protein (PTHrP)) stimulate bone formation (and subsequently bone resorption), thereby increasing BMD. 

In postmenopausal women with osteoporosis, the primary outcome investigated in clinical trials is the reduction of fracture. Treatments have been shown to reduce the risk of hip fracture up to 40%, vertebral fractures by 30-70% and some compounds reduce the risk for non-vertebral fractures up to 30-40%. 
Derived from randomized controlled trials, anti-fracture efficacies of the most frequently used treatments for postmenopausal osteoporosis when given with calcium and vitamin D supplements are indicated in the table below.

Table published in the  2nd edition of the Compendium of Osteoporosis [1]Cramer, J.A., et al., A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int, 2007. 18(8): p. 1023-31.

In men and in glucocorticoid-treated populations, regulatory approval has been obtained on the basis of bridging studies in which similar BMD changes to those seen in postmenopausal women with osteoporosis have been demonstrated.

Treatment options can only work if taken as recommended. It is common for patients with osteoporosis to find taking medication challenging. This jeopardizes the anti-fracture efficacy and the cost-effectiveness of the treatment. Adherence to oral bisphosphonates is especially low, as low as 43-59% at 1 year and appears to be worse with generic medications [1]Cramer, J.A., et al., A systematic review of persistence and compliance with bisphosphonates for osteoporosis. Osteoporos Int, 2007. 18(8): p. 1023-31.

[2]Kothawala, P., et al., Systematic review and meta-analysis of real-world adherence to drug therapy for osteoporosis. Mayo Clin Proc, 2007. 82(12): p. 1493-501.

. As a result, up to half of all people stop their treatment after only one year. 

As osteoporosis is asymptomatic for most patients, and treatment efficacy is undetectable by them, effective communication between healthcare professionals and patients and early detection of non-adherence are required to improve patient’s adherence. 

A screening strategy has been proposed based on the response of biochemical markers of bone turnover (PINP and CTX) after 3 months of therapy of oral bisphosphonates. Assays of bone turnover markers are widely available, affordable and physicians are used to require these assays and to interpret the results. Blood changes of bone markers reflect early effects of the therapy on the bone tissue. Bone formation marker, serum PINP (procollagen type I N-terminal propeptide) and bone resorption marker, serum CTX (collagen type I C-terminal telopeptide) have been recommend as the reference markers by the International Osteoporosis Foundation (IOF) and the International Federation of Clinical Chemistry (IFCC) [3]Vasikaran, S., et al., Markers of bone turnover for the prediction of fracture risk and monitoring of osteoporosis treatment: a need for international reference standards. Osteoporos Int, 2011. 22(2): p. 391-420.

. If a significant decrease is observed, the treatment can continue. If no change is observed, the physicians should reassess the adherence to treatment and also other potential issues with the treatment [4]Diez-Perez, A., et al., International Osteoporosis Foundation and European Calcified Tissue Society Working Group. Recommendations for the screening of adherence to oral bisphosphonates. Osteoporos Int, 2017. 28(3): p. 767-774.

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In addition to drug therapy, calcium and vitamin D supplements can be prescribed to ensure maximum effectiveness of the medication. 
Health care professionals and patients should also be aware that attention to lifestyle factors (including risk factors, nutrition and exercise) must go hand in hand with any drug treatment prescribed. 

Each class of medications has different mechanisms of action and its distinct profile of side effects. These are described with each medication. For patients at risk of a side effect, the physician selects the most appropriate treatment, if possible avoiding the one causing the side effect. For people at high risk of fracture, the benefit of a treatment in decreasing the risk of fracture far outweigh the risk of serious side effects. 

The two main rare adverse events observed patients taking bisphosphonates and denosumab are atypical femoral fracture and osteonecrosis of the jaw. Read more about these in the side effects section. 

Practical and emotional support is important for a person on osteoporosis treatment. This can be provided by health professionals, osteoporosis patient support groups, family and friends. Such support is of great assistance in helping people manage their osteoporosis, and in lessening the feelings of isolation and depression experienced by many patients with severe osteoporosis. Read more about practical support for patients.

IOF and the Bone Health and Osteoporosis Foundation (BHOF) have developed a clear and simple tool aiming to help primary care providers initiate a dialogue with their patients about osteoporosis and fracture risk. It is intended to be used during medical consultations to improve patients’ understanding of their condition and provide them with essential information about anti-osteoporosis medications and their relative risks and benefits.

Resources

• Printable communication tool
  • English, Spanish, French, German, Japanese
  • English (BHOF USA)
•  Instructions on how to use the communication tool effectively in communications with patients
  • English, Spanish, French, German, Japanese
• Infographic: "How to communicate effectively with patients about fracture risk and osteoporosis treatment”
  • English, Spanish

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