Osteoporosis guidelines (21 July 2011) - Hampshire Hospitals NHS ...

Basingstoke, Southampton and Winchester
District Prescribing Committee
Medical Management of Men and Women over 45yrs who have
or are at risk of Osteoporosis
Frail,
increased
fall risk +
housebound
Risk Factors
Is bone density assessment clinically indicated?
Previous fragility fracture
Advise calcium
1 – 1.2 gram and
colecalciferol 20
micrograms (800IU)
daily
Yes
Consider using FRAX & NOGG recommendations
Assess fracture risk using Frax ® tool
http://www.shef.ac.uk/FRAX
then
using the link to NOGG guidance:
Investigations 1
Age 75yrs Age 75yrs
Assess falls risk.
Advise or refer to
Falls Service as
appropriate
Reas sure,
General measures 3 ,
Reassess in < 5 yrs
depending on
clinical context
Measure BMD
then recalculate
fracture risk to
determine if
intervention is
appropriate.
Consider
treatment
Measure BMD (DXA scan, hip + spine)
Normal
T score
‣ above -1
Osteopenia
T score -1 to -2.5
Reassure General Measures 3
General
Me asures 3
Osteoporosis 2
T score below –2.5
Advise Treatment
ALENDRONATE 70mg WEEKLY (1st Line)
(Advise three/six monthly review of adherence to
therapy as non-compliance is common. Seek
specialist opinion if patient sustains a fracture after 1
year on compliant therapy)
1
All Patients
‣ FBC, ESR (If ESR raised, measure
serum paraproteins and urine
Bence Jones protein)
‣ Bone and liver function tests (Ca,
P, Alk phos, albumin, ALT)
‣ Renal function
‣ Serum 25 0H Vit D and consider
PTH if:
If Calcium level raised
If calcium level in upper
quartile of normal range and
vitamin D deficient
2 nd Line
If patient unable to comply with the special instructions for the administration of
alendronate, or has a contraindication to, is intolerant of, or has a lack of clinical
response to alendronate
ALTERNATIVE
BISPHOSPHONATE
DENOSUMAB
60mg s.c.
injection
6 monthly
STRONTIUM
2 g at night
RALOXIFENE
60mg daily
Additional tests if indicated:
‣ Serum TSH.
‣ Lateral thoracic and lumbar spine
X rays
‣ Isotope bone scan
‣ Serum testosterone, LH and
SHBG, PSA (men)
‣ BMD if monitoring required
‣ Consider GT
‣ Coeliac screen (TTG)
Refer to Table A on
Page 5
Specialist Initiated
Amber Drug
see
Shared Care
Guidelines*
Teriparatide
Intravenous bisphosphonates
Denosumab
3
General measures
‣ Recommend good nutrition esp.
with adequate vitamin D
‣ Recommend regular weight
bearing exercise
‣ Maintain ideal body weight
‣ Avoid tobacco use and alcohol
abuse (> government
recommendations)
‣ A ssess falls risk and give advice if
appropriate
All patients must be prescribed
Calcium 1 – 1.2 gram + colecalciferol 20 micrograms (800 IU) daily
unless clinician is confident patient has adequate calcium intake and is vitamin D replete
General Measures 3
2 Consider treatment depending on age and fracture probability.
* Denosumab Shared Care Guideline accessed at: www.hampshire.nhs.uk/primary-care on
Pages4PrimaryCare website, Prescribing Folder in GP & Pharmacist sections.
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Basingstoke, Southampton and Winchester
District Prescribing Committee
ALGORITHM FOR THE MEDICAL MANAGEMENT OF GLUCOCORTICOID-INDUCED
OSTEOPOROSIS IN ADULTS
Glucocorticoid therapy expected to be 3months
or
Cumulative dose equivalent to 1.5gram per year for
patients prescribed repeated short courses)
Age 65yrs
Age 65yrs
No
previous
fragility
fracture
Previous fragility
fracture or incident
fracture
Investigations 1
Measure BMD
(DXA scan, hip + spine
T score above 0
Reassure
General
measures 3
Repeat BMD
not indicated
unless a daily
dose of 10mg
or more is
required
T score between
0 and - 1.5
General
measures 3
Repeat BMD in
1 – 3 yr if
glucocorticoids
continued
T score
– 1.5 or lower 2 Treatment
RISEDRONATE 35mg WEEKLY
(or other bisphosphonate if not
tolerated)
All patients must also be prescribed:
Calcium 1 – 1.2 gram + colecalciferol 20 micrograms
(800 IU) daily
unless clinician is confident patient has adequate
calcium intake and is vitamin D replete
Initiate osteoporosis management when
glucocorticoid is started and stop treatment six
months after glucocorticoids stop.
Advise three/six monthly review of
adherence to therapy.
1
All Patients
‣ FBC, ESR (If ESR raised, measure serum
paraproteins and urine Bence Jones protein)
‣ Bone and liver function tests (Ca, P, Alk phos,
albumin, ALT)
‣ Renal function
‣ Serum 25 0H Vit D and consider PTH if:
If Calcium level raised
If calcium level in upper quartile of
normal range and vitamin D deficient
Additional tests if indicated:
‣ Serum TSH.
‣ Serum 25 0H Vit D
‣ Lateral thoracic and lumbar spine X rays
‣ Isotope bone scan
‣ Serum testosterone, LH and SHBG, PSA (men)
‣ BMD if monitoring required
‣ Consider GT
‣ Coeliac screen (TTG)
2
Consider treatment depending on age and fracture probability
3
General measures
‣ Reduce dose of glucocorticoid when possible,
‣ Consider glucocorticoid sparing therapy if appropriate
or consider alternative route of administration
‣ Recommend good nutrition esp. with adequate calcium
and vit D
‣ Recommend regular weight bearing exercise
‣ Maintain ideal body weight
‣ Avoid tobacco use and alcohol abuse (> government
recommendations)
‣ Assess falls risk and give advice if appropriate
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Basingstoke, Southampton and Winchester
District Prescribing Committee
Medical Management of men and women over 45yrs who have
or are at risk of Osteoporosis
CLINICAL RISK FACTORS FOR OSTEOPOROSIS
Previous fragility fracture*
Predisposing medical
Current glucocorticoid use ≥ 3 months*
conditions
Parental history of hip fracture*
hyperthyroidism
Radiographic osteopenia*
rheumatoid arthritis
Height Loss 3.0 – 5.0 cm*
type 1 diabetes
Female hypogonadism
‣ post-menopause
‣ untreated premature menopause
‣ drug or surgically induced menopause
‣ premenopausal amenorrhoea ≥6 months, (excl pregnancy)
inflammatory bowel
disease
malabsorption/coeliac
disease
prolonged immobility
Body Mass Index ( 3 units alcohol daily
Male hypogonadism ***
Drugs associated with osteoporosis
‣ excessive levothyroxine replacement therapy
‣ long-term heparin
‣ anticonvulsants
‣ antipsychotics
‣ Depo-Provera, 2yrs treatment
‣ Aromatase inhibitors**, GnRH analogues*** (separate guidance)
* Risk factors that clinically indicate a direct Bone Mineral Density assessment.
** Aromatase inhibitor guidance available as algorithms in Appendix 1 to this guideline 1 .
*** The use of GnRH analogues in men is associated with bone loss and fractures but there is no official
guideline to date on its management. Recommend BMD after initiation of therapy (when any additional
secondary causes of bone loss are ruled out) and consider bisphosphonate or denosumab therapy for men
with osteoporosis and fragility fractures, or men with a T score -2.5 SD or lower. Also consider treatment for
men with a T score between -1 and -2.5 SD on GnRH analogues if additional risk factors were present. All
should have adequate intake of calcium and be vitamin D replete or be prescribed supplementation and a have
a follow-up BMD in 1 – 2 years 2 .
The FRAX® tool is an algorithm which calculates fracture risk. (Available at www.shef.ac.uk/FRAX & it links
to guidance published by the National Osteoporosis Guideline Group (NOGG) 3 for the management of
osteoporosis).
Therapeutic Agents Available For The Management Of Osteoporosis
(See Table A for anti-fracture efficacy of therapies available)
Refer to the latest data sheet for full prescribing details about use in elderly, renal and hepatic
impairment, contraindications, precautions etc.
Refer to the BNF- Guidance on prescribing in renal impairment- for advice on using eGFR /
calculated creatinine clearance to adjust doses for patients with renal impairment.
CALCIUM AND VITAMIN D 3
Adequate levels of calcium and vitamin D 3 (colecalciferol) are required to ensure optimum effects of all the
treatments for osteoporosis. Unless the clinician is confident that the patient has adequate calcium intake
and is vitamin D replete, calcium and colecalciferol supplementation at a dose of Calcium 1 – 1.2 gram
(equivalent to 2.5 – 3.0g Calcium Carbonate) and colecalciferol 20 micrograms (800 IU) daily should be
prescribed. Avoid colecalciferol in severe renal impairment as it cannot be converted to its active
form in the renally impaired.
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BISPHOSPHONATES
Alendronate is the first choice bisphosphonate for the majority of patients
Risedronate may be prescribed, in patients intolerant of alendronate, in young adults and in
patients with glucocorticoid-induced osteoporosis - may be beneficial due to rapid ‘off’ effect
For other bisphosphonates choices see Table A for site specific anti-fracture efficacy
Intravenous bisphosphonates may be used under specialist guidance
Oral bisphosphonates should be swallowed whole with a glass of water 30-60 minutes before the first food
or drink (other than water) of the day. Patients should stand or sit upright (not lie down) for at least 30
minutes post dose.
Discontinue treatment if oesophageal ulceration, erosion, stricture, or severe lower gastrointestinal
symptoms occur.
Bisphosphonates should be avoided in patients with moderate to severe renal impairment. ( eGFR
< 35ml / minute for alendronate, < 30ml / minute for risedronate).
Atypical femoral fractures (often bilateral) have been reported rarely with bisphosphonate therapy,
mainly in patients receiving long-term treatment for osteoporosis. Patients should be advised to report any
thigh, hip or groin pain. Discontinuation of bisphosphonate therapy in patients suspected to have an
atypical femur fracture should be considered while they are evaluated, and should be based on an
assessment of the benefits and risks of treatment. For general advice on duration of therapy see separate
section ‘Duration of Treatment’ on page 5 of the guidelines.
Osteonecrosis of the jaw has been reported rarely with IV bisphosphonate use and very rarely with oral
use. Adequate oral hygiene should be maintained during and after bisphosphonate treatment. Ideally in
patients with concomitant risk factors e.g. cancer, chemotherapy treatment, glucocorticoid treatment, or
poor oral hygiene, remedial dental work should be completed before starting bisphosphonates.
STRONTIUM RANELATE
Indicated, when bisphosphonates are contra-indicated or cannot be tolerated, or the patient has difficulty
complying with their strict ingestion regimen.
Also consider for
women aged over 80 years for the primary prevention of fragility fractures
women aged 75 years or older with a previous fragility fracture
Strontium should be taken at bedtime at least 2 hours after food and /or milk.
Avoid in severe renal impairment ( eGFR 30ml/min).
Severe allergic reactions including DRESS (drug rash with eosinophilia systemic symptoms) have been
reported in patients taking strontium. If a rash develops, treatment must be stopped immediately. The risk
of severe allergic reactions can be life-threatening and strontium must not be re-introduced. Symptoms can
be improved by glucorticoid therapy but recovery can be slow and there is a risk of symptoms returning
during the recovery period.
Risk of thrombo-embolism is increased so assess predisposing conditions prior to use
RALOXIFENE
For postmenopausal women with vertebral osteoporosis, with an unsatisfactory response to or an
intolerance of bisphosphonates. Avoid in severe renal impairment.
TERIPARATIDE (Specialist Use only)
Indications restricted to patients with an unsatisfactory response/intolerance to the above therapies AND
aged > 65 yrs old who have a T score of –4 SD or below OR
aged > 65 yrs old who have a T score of -3.5 SD or below plus at least 2 fractures OR
aged 55 – 64 yrs old who have a T score of -4 SD or below plus at least 2 fractures
Use with caution in moderate renal impairment. Contraindicated in severe renal impairment.
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DENOSUMAB (Specialist Initiated AMBER drug)
(Shared Care Guidelines at www.hampshire.nhs.uk/primary-care on Pages4PrimaryCare website, Prescribing Folder in GP & Pharmacist
sections).
For the secondary prevention of osteoporotic fragility fractures in postmenopausal women at
increased risk of fractures who are unable to comply with the special instructions for the
administration of oral bisphosphonates, are intolerant of oral bisphosphonates or for whom
treatment with oral bisphosphonates is contraindicated.
Administered as a 60mg subcutaneous injection at 6 month intervals
No dose adjustment required in patients with renal impairment.
Ensure calcium levels are within the normal range prior to initiation of, and during therapy.
N.B. To decrease the possibility of duplication of bone protection prescribing it is essential
that;
a) secondary care inform the patient’s GP of the date denosumab therapy was initiated
and
b) primary care are advised that these details are included in the patient’s repeat medication records
and entered onto practice recall system for recall at 6 month intervals.
The following conditions may be associated with denosumab treatment: eczema, diverticulitis, cataracts,
hypocalcaemia, and skin infections (predominantly cellulitis). The SPC states that osteonecrosis of the jaw
has been reported in patients receiving denosumab or bisphosphonates with most cases occurring in
cancer patients; however some have occurred in patients with osteoporosis.
HORMONE REPLACEMENT THERAPY
only recommended as treatment for the prevention of osteoporosis in women with a premature
menopause, and only prescribed in women up to 50 years of age.
COMBINATION THERAPY
(not including combinations with Calcium and colecalciferol)
is not routinely prescribed but may be rarely used under specialist recommendation only.
DURATION OF TREATMENT
Oral bisphosphonates, strontium ranelate and raloxifene are recommended for up to five years of
treatment followed by re-evaluation of the individual patient. DXA scan or evaluation of biochemical
markers of bone turnover can be considered after this period. After five years of treatment, for patients not
considered at high risk of fracture, a “drug holiday period” of up to three years without therapy can be
considered. (N.B Ensure patient is calcium and vitamin D replete, or continue adequate supplementation).
In other circumstances, it appears safe to continue for a further five years of treatment. Teriparatide should
be used for up to 18 months, and denosumab for up to 3 years in the first instance.
TABLE A 3
Effect of major pharmacological interventions on fracture risk when
given with calcium and vitamin D in postmenopausal women with osteoporosis
Intervention Vertebral Non-vertebral Hip
Alendronate A A A
Risedronate A A A
Zoledronate A A A
Denosumab A A A
Strontium ranelate A A A
Ibandronate a A A nae
Raloxifene A nae nae
PTH (1-84) A nae nae
Teriparatide A A nae
in subsets of patients only (post-hoc analysis)
a
Injection only available on Formulary
nae : not adequately evaluated
PTH : recombinant human parathyroid hormone
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Table A 3
Grading of recommendations and evidence levels
Levels of evidence for studies of intervention are defined as follows:
Ia from meta-analysis of randomised controlled trials (RCTs)
Ib from at least one RCT
IIa from at least one well designed controlled study without randomisation
IIb from at least one other type of well designed quasi-experimental study
III from well designed non-experimental descriptive studies, eg comparative
studies, correlation studies, case-control studies
IV from expert committee reports or opinions and/or clinical experience of
authorities
The validity of candidate risk factors is also assessed by an evidence-based approach:
Ia Systematic reviews or meta-analysis of level I studies with a high degree of homogeneity
Ib Systematic reviews or meta-analysis with moderate or poor homogeneity
Ic Level I studies (with appropriate populations and internal controls)
IIa Systematic reviews or meta-analysis of level II studies
IIb Level II studies (inappropriate population or lacking an internal control)
IIIa Systematic reviews or meta-analysis of level III studies
IIIb Case-control studies
IV Evidence from expert committees without explicit critical scientific analysis or that based on
physiology, basic research or first principles.
The quality of the guideline recommendations is similarly graded to indicate the levels of
evidence on which they are based:
grade A evidence levels Ia and Ib
grade B evidence levels IIa, IIb and III
grade C evidence level IV
References
1. Reid DM, Doughty J, Eastell R et al. Guidance for the management of breast cancer treatment-induced
bone loss: a consensus position statement from a UK Expert Group. 2008. Cancer Treat Rev 2008; 34:
S1– S18.
(Full guidance and 2 treatment algorithms available at www.nos.org.uk/NetCommunity/Document.Doc?id=124
and the algorithms are also contained in Appendix 1 of this document.
2. Greenspan S. Approach to the Prostate Cancer Patient with Bone Disease. J Clin Endocrinol Metab.
Jan 2008, 93(1):2-7
3. Guideline for the diagnosis and management of osteoporosis in postmenopausal women and men from the
age of 50 years in the UK. Produced by J Compston, A Cooper, C Cooper, R Francis, JA Kanis, D Marsh,
EV McCloskey, DM Reid, P Selby and M Wilkins, on behalf of the National Osteoporosis Guideline Group
(NOGG). October 2008 and updated July 2010 (www.shef.ac.uk/NOGG/ )
4. Bone and Tooth Society of Great Britain, National Osteoporosis Society, Royal College of Physicians
“Glucocorticoid – induced Osteoporosis: Guidelines for Prevention and Treatment” London: RCP, 2002
5. Bone and Tooth Society of Great Britain, National Osteoporosis Society, Royal College of Physicians
‘‘Clinical Guidelines for the prevention and treatment of Osteoporosis’’ London RCP Update 2000
6. Reginster JY, Seeman E, De Vernejoul MC et al. Strontium ranelate reduces the risk of nonvertebral
fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS)
study. J Clin Endocrinol Metab.2005 May; 90(5):2816-22.
7. Meunier PJ, Roux C, Seeman E, et al. The effects of strontium ranelate on the risk of vertebral fracture in
women with postmenopausal osteoporosis. N Engl J Med. 2004 Jan 29; 350(5):459-68.
8. NICE Technology Appraisal TA161 – Alendronate, etidronate, risedronate, raloxifene, strontium ranelate
and teriparatide for the secondary prevention of osteoporotic fragility fractures in postmenopausal women.
October 2008.
9. NICE Technology Appraisal TA160- Alendronate, etidronate, risedronate, raloxifene and strontium ranelate
for the primary prevention of osteoporotic fragility fractures in post menopausal women. October 2008.
10. NICE Technology Apprasal TA 204 -Denosumab for the prevention of osteoporotic fractures in
postmenopausal women. October 2010.
Prepared by:
Approved by:
Date:
Kathleen Hayes, Pharmacist ,Falls Team, Solent NHS Trust, in collaboration with Prof. C Cooper,
Professor of Rheumatology, Dr E Dennison, Consultant Rheumatologist, University of
Southampton School of Medicine, Dr Gill Pearson, Associate Specialist in Rheumatology,
Southampton, Dr Annie Cooper, Consultant Rheumatologist, Winchester, Dr Peter Prouse,
Consultant Rheumatologist, Basingstoke.
Basingstoke Southampton and Winchester District Prescribing Committee
July 2011 Renewal date July 2012
6 of 6 pages

Reid DM, Doughty J, Eastell R, Heys SD, Howell A, McCloskey EV, Powles T, Selby P, Coleman RE. Guidance for the management of breast cancer treatmentinduced
bone loss: a consensus position statement from a UK Expert Group. 2008. Cancer Treat Rev 2008;34:S1–S18.
Appendix 1 Management of bone loss in early breast cancer