HILLINGDON PRIMARY CARE TRUST GUIDELINES FOR THE MANAGEMENT OF OSTEOPOROSIS & MENOPAUSAL SYMPTOMS - December 2008 Definitions

WHO definition of osteoporosis: A disease characterised by low bone mass and microarchitectural deterioration of bone tissue, leading to enhanced bone fragility and consequent increase in fracture risk. Osteoporosis is caused by an imbalance between the relative rates of bone resorption and formation. Climacteric is the process (natural or iatrogenic) that occurs over a period of years in a woman's late 40s or early 50s when her supply of ovarian follicles declines and her menstrual cycle becomes irregular and / or stops completely.

Incidence: 1 in 3 women and 1 in 8 men aged over 50

Major Risk Factors for Osteoporosis

1. Previous low trauma or fragility fracture (Strong risk for future fracture so treatment should be started whilst waiting for scan) 2. Oestrogen deficiency in women: menopause or hysterectomy <45 years, secondary amenorrhoea > 6 months not due to pregnancy, primary hypogonadism 3. Family history: maternal hip fracture 4. X-ray evidence of osteopenia 5. Primary or secondary hypogonadism in men 6. Low BMI (<19kg/m2), height loss, kyphosis 7. Secondary osteoporosis: primary hyperparathyroidism, hyperthyroidism, poorly controlled thyrotoxicosis, malabsorption, inflammatory arthritis, liver disease, alcoholism. 8. Patients currently on drugs such as steroids ( > 5mg prednisolone/day for 3 months or more), chemotherapy and long term warfarin or anticonvulsants. 9. Poor mobility (see risk factors for recurrent falls) ---------------------------------------------------------------------------------------------------------------------------10. Smoking & heavy drinking are risk factors only if additional to risks 1 to 9.

Peripheral DEXA Scans

All patients with risk factors should have BMD assessments carried out via peripheral DEXA scans. These forearm or heel scans are mobile, so more easily obtained that the gold standard DEXA scans. They are well validated techniques (Blake et al). The same clinical decision would be made no matter which skeletal site is measured (Nelson et al). Peripheral DEXA scans are useful for initial screening purposes for gold standard DEXA scan candidates. The gold standard measures BMD at the hip & spine and is more strongly predictive of hip fractures than BMD assessments at peripheral sites (Black et al).
N.B.

1. 2.

There is no need to scan patients 75 yrs & above prior to starting treatment if they have sustained minor trauma fracture. They need blood tests to rule out causes of secondary osteoporosis. Peripheral scans are of no use in monitoring effects of treatment.

Investigations
The following baseline investigations should be done for patients over 65 years with a diagnosis of osteoporosis where indicated: FBC (for malabsorption), ESR or plasma viscosity (for myeloma) Bone profile & liver function tests -Ca, P, alk phos, albumin, AST/gamma GT ( for liver disease) Serum creatinine (for kidney disease) Serum TSH (for hyperthyroidism) Serum parathormone Testosterone & SHBG (serum human binding globulin)for all men (for gonadal failure) Protein electrophoresis & Bence Jones Protein in 24 hour urine for everyone with frank osteoporosis on peripheral scan (for multiple myeloma) Serum vitamin D in Indian sub-continent patients & others from high risk group. 1

Gold Standard DEXA Scans

1. For patients whose peripheral
DEXA scan reveals T score of 1.4 to 2.6 with major risk factors, and for women who do not or cannot take HRT prevention, or men with fracture risk (excluding <80 yrs (NOS Position Statement) For patients with history of fracture while taking bisphosphonates.

2.

WHO Classification of BMD T-scores Gold Std at hip & spine

Low risk Medium risk High risk Young adult mean Osteopenia low bone mass, suitable for bone-loss prevention treatment Osteoporosis High fracture risk Severe osteoporosis very low T-score PLUS at least one vertebral fracture 0 to -1 -1 to -2.5 Less than - 2.5

General Measures on Prevention of Osteoporosis

(All patients with osteoporosis and at risk of osteoporosis)

Dietary advice: balance with adequate protein and calcium - 1200 to 1500mg daily Lifestyle advice e.g. weight bearing exercise such as a brisk walk, treadmill and stair climbing. Physiotherapy for improvement of balance and muscle strengthening especially for people with poor mobility & recurrent falls.

Hip protectors: Useful for frail elderly patients (over 80 years) at high risk of falling. Cost~ 35. NB: May be cumbersome to put on.

Pharmacological Treatment of Osteoporosis Primary care

FEMALES 1. Bisphosphonates Generic alendronic acid or risedronate (See pg 3)

Secondary Care
(Not in any order of choice)

2.

Strontium ranelate for those unable to tolerate or unwilling to take bisphosphonates or where HRT is contraindicated 3. HRT for women First line for women with premature menopause up to age 50 and for women over 50 with menopausal symptoms & osteoporosis. (Absolute contra-indications: breast ca, DVT, ischaemic heart disease, CVA, TIA, active endometrial cancer) 4. Additional therapy: Calcium & Vitamin D Analgesia where osteopenic fracture is suspected Simple analgesics, NSAIDs, lumbar supports, TENS ALL FRACTURE PATIENTS 1. Bisphosphonates 2. Strontium 3. Additional therapy: Calcium & Vitamin D for patients over 80 years DEXA scans are of no value for this age group.
4. 5.

Calcitonin nasal spray or injection Fluoride Anabolic steroids Vitamin D metabolites & analogues Pamidronate IV Infusion Raloxifene Teriparatide (PTH)
( PBR-excluded 09/10)

Zolendronic acid Ibandronic acid

Analgesia (as above) Ibandronic acid IV in patients intolerant to oral bisphosphonates

Pharmacological Treatment Continued (1) Hormonal Replacement Therapy

The drug treatments recommended in Appendix A retard bone loss and are evidence-based and costeffective.

HRT doses for prevention of osteoporosis - 2mg oral oestrogen, 0.625mg conjugated equine oestrogen, 50mcg patch.

(2) Bisphosphonates - (Alendronic acid & Risedronate)

The drug treatments recommended below retard bone loss, reduce fracture risk, and are evidence-based & cost-effective. Bisphosphonates inhibit bone turnover & reduce the risk of bone fracture. They are licensed for the treatment & prevention of osteoporosis in post-menopausal women. This is the treatment of choice where there is a significant osteoclastic asctivity causing increased resorption.

Generic alendronic acid 10mg daily / Generic alendronic acid 70mg once a week or Risedronate 5mg od / Risedronate 35mg weekly (3) Strontium ranelate 2g sachet daily in water on an empty stomach 2 hours after evening meal. (4) Calcium supplements
For dietary-deficient calcium or patients with malabsorption syndrome and poor mobility Supplements of 1g or more daily decrease bone loss in elderly women, but the effects are less marked than those of HRT & bisphosphonates. There is evidence to show a reduction of vertebral fractures with calcium alone, but most of the evidence for anti-fracture efficacy has been obtained with calcium in combination with Vitamin D. Adcal-D3 Two tablets daily or Calcichew D3 Forte

Referral to Secondary Care

Initial Assessment Referrals

History of thrombosis or strong family history of thrombosis where HRT is being considered Any post-menopausal bleeding with unconfirmed diagnosis where HRT is being considered Breast lump with unconfirmed diagnosis where HRT is being considered

Perimenopausal women persistent post-coital bleeding / or persistent inter-menstrual bleeding where HRT is being considered Significant abnormalities from baseline investigations secondary cause of osteoporosis Patients with secondary cause e.g. multiple myeloma or malabsorption, which needs investigation and treatment should be referred to appropriate consultant.

Patients Already on Treatment

Patients who develop a breast lump after initiating therapy with HRT Sequential HRT persistent heavy period for > 6 months Continuous combined therapy Bleeding 6 months after becoming completely ammenorheic (it may take 6-10months after initiation to become ammenorheic and slight irregular bleeding during this stage is acceptable)

Perimenopausal women persistent post-coital bleeding / or persistent inter-menstrual bleeding Treatment resistant osteoporosis second DEXA scan 2 years later
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 Patients with complications such as multiple co-morbidities Patients not tolerating or have contraindications to oral bisphosphonates and/or strontium Patients who have sustained fragility fracture whilst on osteoporosis treatment with good compliance.

Monitoring

Patients on HRT
Monitoring should be undertaken at 3 months after starting HRT and then every 6 months Menopausal symptom control Bleed pattern (non-hysterectomised women) Day of onset and duration Amount of flow Any breakthrough bleeding Side-effects and their management Health education and advice Smoking, diet and exercise Self breast awareness Regular attendance for breast and cervical screening Stress management BMI and BP Contraceptive advice, if applicable Review treatment strategy and continued need for HRT Women with history of endometriosis or fibroids should receive careful supervision, including a regular clinical pelvic examination and pelvic ultra sound. After 5 years on HRT beyond the age of 50 an individual risk benefit assessment should be made to decide if HRT should be continued. This exercise should be repeated after 10 years HRT use after the age of 50.

Patients on Bisphosphonates and /or Strontium

Routine monitoring of patients on these drugs is not recommended unless a patient sustains a fragility fracture whilst on treatment. Patients with an osteopenic T score on forearm DEXA should be referred for hip and spine DEXA scan (Gold standard) if they develop additional risk factors.

Assessing the Risk of Falls and Appropriate Intervention

Patient risk factors Balance, gait or mobility problems (including joint disease, stroke and Parkinson's disease) Polypharmacy i.e. taking four or more medicines, particularly centrally sedating or blood pressure lowering drugs. Visual impairment. Impaired cognition or depression. Postural hypotension. Environment risk factors Poor lighting, particularly on the stairs. Loose carpets or rugs. Badly fitting footwear or clothing. Lack of safety equipment e.g. grab rails. Steep stairs and slippery floors Inaccessible lights or windows. Older people who fall should be recalled to the surgery or assessed in their homes for review, particularly those who: Have previous fragility fractures Have attended accident and emergency following a fall Have called an ambulance following a fall Have two or more patient risk factors Have frequent unexplained falls Fall in hospital or in a nursing or residential home Live in unsafe housing conditions Are very afraid of falling Interventions to reduce the risk of falls and injury from falling: Assessment and correction of vision, if possible Correction of postural hypotension Medication review and discontinuation of inappropriate medication Rehabilitation, including physiotherapy, to improve confidence Occupational therapy to identify and correct hazards in the home Repairs and improvements to the home Exercise and balance training Use of hip protectors Treatment of osteoporosis

APPENDIX A ______________________________________________________________________________
TABLE A Sequential Preparations - To be used for: Perimenopausal women with intact uteri.

Tablets
Elleste Duet Oestradiol 2mg + Norethisterone 1mg (C19) Prempak C Conj Oestrogens (equine)1.26mg+ Norgestrel 150mcg

Patches
Evorel Pak (patch & tab) oestradiol 50mcg + Norethisterone 1mg (C19)

Reasons to Commence / Switch

Patches preferred if malabsorption, colitis, coeliac disease, abnormal liver function. Also for persistent side-effects on tablets.

Switch from (C19) to (C21) if acne / oily skin, hirsuitism, mood changes, history of Femapak (patch & severe PMT. tab) Avoid (C21) if history of depression, inc. Femoston Oestradiol 80mg + post-natal depression. Oestradiol 2mg + Dydrogesterone 10mg Persistent breast tenderness / headaches: Dydrogesterone 10mg (C21) (C21) reduce dose of oestrogen, switch to patch Premique Cycle Evorel Sequi (patch) or switch type of oestrogen. Conj. equine oestr. 0.625mg + Oestradiol 50mcg + Medroxyprogesterone 5mg (C21) Norethisterone NB: Switch from oral to non-oral prep if 170mcg (C19)
LFTs are raised, or if patient is a diabetic with triglyceride >2.3

TABLE B Continuous combined Preparations - To be used when: Period free HRT is required patients should be amenorrhoeic for >1 year or > 54 years of age. Tablets Elleste Duet Conti Oestradiol 2mg + Norethisterone 1mg (C19) Femoston Conti Oestradiol 1mg + Dydrogesterone 5mg (C21) Kliovance Estradio 1mg + norethisterone 500mcg (C19) Premique Conj. equine oestr. 0.625 + Medroxyprogesterone 5mg (C21) Indivina Estradiol valerate + Medroxyprogesterone
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Patches Evorel Conti Oestradiol 50mcg + Norethisterone 170mcg (C19)

Reasons to Commence / Switch Patches preferred if malabsorption, colitis, coeliac disease, abnormal liver function. Also for persistent side-effects on tablets. Switch from (C19) to (C21) if acne / oily skin, hirsutism, mood changes, history of severe PMT. Avoid (C21) if history of depression, inc perinatal depression. Persistent breast tenderness / headaches: reduce dose of oestrogen, switch to patch or switch type of oestrogen.

Livial Tibolone 2.5mg Use when others not tolerated

Reserve tibolone for patients with low libido, breast tenderness or breakthrough bleeding not resolved by dose and formulation changes.

TABLE C

Unopposed Oestrogen - To be used ONLY if patient is hysterectomised Patches Evorel oestr. Oestradiol 50mcg, 75mcg, 100mcg Reasons to Commence / Switch Patches preferred if malabsorption, colitis, coeliac disease, abnormal liver function. Also for persistent side-effects on tablets.

Tablets Premarin Conj. equine 0.625mg

Elleste Solo Oestradiol 1mg & 2mg micronised Climaval Estradiol 1mg & 2mg Zumenon Estradio 1 and 2mg

TABLE D

Topical - To be used for : Relief of vaginal symptoms and bladder symptoms (urgency and urge incontinence)

Ortho-gynest cream or pessary (oestriol) Lowest possible dose and discontinued as soon as possible. Review every 3-6 months. To avoid systemic absorption, recommend use daily for 2 weeks, then twice a week for 3 months, then once a week if bladder symptoms recur. It treatment is required for more than 3 months twice weekly, patients should be prescribed an oral progestogen daily to combat endometrial hyperplasia.

SIDE EFFECTS OF HRT Oestrogenic side effects Progestogenic side effects

Breast tenderness Irregular bleeding Water retention Weight gain Mild depression Irritability Abdominal bloating Acne Hirsutism

APPENDIX B

Hillingdon Osteoporosis Guideline Development Group

MEDICAL MANAGEMENT OF PATIENTS AT RISK OF OSTEOPOROSIS (10.11.08)

Risk Factors

Frail, increased risk, + / - housebound

Previous fragility fractures for under 75 years (Over 75s no need for scan before treatment is started)

Investigations Measure BMD with Peripheral Scanner

Normal T score 0 to -1.4

Osteopenia T score -1.4 to -2.6

Osteoporosis T score below -2.6

Reassure Lifestyle advice

Give lifestyle advice Calcium & vitamin D is needed Treat if previous fracture

Lifestyle advice & Pharmacological treatment

Refer for Gold Standard DEXA Scan

1. 2. 3. Patients with history of fracture whilst on treatment with bisphosphonates Osteopenic on peripheral DEXA scan i.e. T score -1.4 to -2.6 Women or men on long term steroids

Calcium & Vitamin D Falls risk: Assessment / advice Consider hip protectors

Previous fragility fractures Previous fragility fractures are a strong independent risk for further fracture. Treat without BMD if medical history is unequivocal in patients 75 years and above

Adapted from the Royal College of Physicians Osteoporosis Report 1999

APPENDIX C

Fracture Index Rating

Useful as a 3-minute questionnaire to identify those at high risk of hip, non-vertebral and vertebral fractures over the subsequent 5 years, and for whom further clinical assessments and intervention are most warranted, to reduce fracture risk. This assessment tool can be used with or without BMD measurements. If the total score is below 6, the patient needs re-assurance & lifestyle advice. If above 6, pharmacological treatment may be required. Question What is your current age? Have you broken any bones after age 50? Has your mother had a hip fracture after age 50? What do you weigh in lbs, stones or kg? Are you currently a smoker? Do you usually need to use your arms to assist yourself in standing up from a chair? If you have a current bone density assessment (BMD), what is the score? Score (0 to 5) 1 for yes 1 for yes 1 for < 125lbs(57kg) 1 for yes 2 for yes 0 to 4

FRAX FRAX is a WHO-supported tool for fracture risk prediction available on www.shef.ac.uk/FRAX. It is an algorithm now used worldwide to express the risk of fracture as a 10 year probability either for a major osteoporotic fracture (hip, wrist, spine or humerus) or a hip fracture. It can be used with or without BMD measurements. Current NICE guidelines do not incorporate the FRAX tool for fracture risk prediction, but it is hoped that this will be available soon.

Updated by: Dr. Krishna Sethi, Hillingdon GP Vasundra Tailor, Head of Medicines Management
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Issued: December 2008 Valid until: December 2010

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