Prevalence and Risk Factors of Osteonecrosis of the Jaw in Patients with Bisphosphonate Exposure in Casablanca, Morocco: An Observational Study

Objective: To study the prevalence of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and to determine the risk factors associated with the occurrence of this pathology. Method: An observational retrospective study was conducted in the Department of Oncology, Rheumatology, and Maxillofacial Surgery of Ibn Rochd University Hospital, Casablanca. The study utilized complete medical records from 2014 to 2022 and included consultations of patients receiving bisphosphonates (BPs) in July and September 2022. Statistical analysis was performed using SPSS version 16.0. Results: Our study population comprised 104 patients, of whom 91% were women and 49% were over 65 years old. Seventy-two percent of patients had a general pathology. Among them, 64 patients were treated with zoledronate, 43 with alendronate, and the remainder with risedronate, ibandronate, and pamidronate. The most common indications for treatment were bone metastasis following breast cancer (29.8%) and osteoporotic fractures (19.2%). Sixty-seven patients received intravenous (IV) treatment;only 10.5% exhibited good oral health. Fifty percent of patients underwent dental treatment, primarily tooth extractions. Osteonecrosis of the jaw (ONJ) was diagnosed in 1.9% of patients, predominantly in stages 1 and 2. Conclusion: Second and third-generation bisphosphonates are more strongly associated with the development of ONJ. Risk factors include monthly IV administration, poor oral health, comorbidities such as diabetes, medications like corticosteroids, invasive dental procedures, and not only oncological conditions but also rare indications such as bone algodystrophy. Nevertheless, our observed prevalence of 1.9% aligns with international rates ranging from 0.8% to 12%. However, most of the studies that have been carried out have been retrospective studies with insufficient numbers of patients. Further prospective epidemiological studies based on standardized protocols with rigorous and appropriate follow-up over several years are essential to determine the exact prevalence of ONJ.

Role of bisphosphonates in osteoporosis caused by adult growth hormone deficiency

In recent years,growth hormone and insulin-like growth factors have become key regulators of bone metabolism and remodeling,crucial for maintaining healthy bone mass throughout life.Studies have shown that adult growth hormone deficiency leads to alterations in bone remodeling,significantly affecting bone microarchitecture and increasing fracture risk.Although recombinant human growth hormone replacement therapy can mitigate these adverse effects,improving bone density,and reduce fracture risk,its effectiveness in treating osteoporosis,especially in adults with established growth hormone deficiency,seems limited.Bisphosphonates inhibit bone resorption by targeting farnesyl pyrophosphate synthase in osteoclasts,and clinical trials have confirmed their efficacy in improving osteoporosis.Therefore,for adult growth hormone deficiency patients with osteoporosis,the use of bisphosphonates alongside growth hormone replacement therapy is recommended.

Impact of bisphosphonate treatment on bone mineral density after kidney transplant

BACKGROUND Mineral bone disease is associated with chronic kidney disease and persists after kidney transplantation.Immunosuppressive treatment contributes to the patho-genesis of this disease.Bisphosphonate treatments have shown positive but inde-finite results.AIM To evaluate the effectiveness and safety of bisphosphonate treatment on post kidney transplantation bone mineral density(BMD).METHODS We included kidney transplant recipients(KTRs)whose BMD was measured after the operation but before the initiation of treatment and their BMD was measured at least one year later.We also evaluated the BMD of KTRs using two valid mea-surements after transplantation who received no treatment(control group).RESULTS Out of 254 KTRs,62(39 men)were included in the study.Bisphosphonates were initiated in 35 KTRs in total(20 men),1.1±2.4 years after operation and for a period of 3.9±2.3 years while 27(19 men)received no treatment.BMD improved significantly in KTRs who received bisphosphonate treatments(from-2.29±1.07 to-1.66±1.09,P<0.0001).The control group showed a non-significant decrease in BMD after 4.2±1.4 years of follow-up after surgery.Kidney function was not affected by bisphosphonate treatment.In KTRs with established osteoporosis,active treatment had a similar and significant effect on those with osteopenia or normal bone mass.CONCLUSION In this retrospective study of KTRs receiving bisphosphonate treatment,we showed that active treatment is effective in preventing bone loss irrespective of baseline BMD.

Role of bisphosphonates in the management of acute Charcot foot

Diabetes mellitus is the most common cause of Charcot neuropathy affecting foot and ankle. Acute Charcot foot(CF) presents with a red and swollen foot in co-ntrast to the painless deformed one of chronic CF. En-hanced osteoclastogenesis plays a central role in the pathogenesis of acute CF. Many studies have shown elevated levels of bone turnover markers in patients with acute CF confirming it. These findings have led cl-inicians to use anti-resorptive agents [bisphosphonates(BP), calcitonin, and denosumab] along with immobi-lization and offloading in acute CF patients. The ma-ximum evidence among all anti-resorptive agents is available for BPs, although its quality is low. Pamidronate has been shown to reduce the markers of activity of CF like raised skin temperature, pain, edema, and bone turnover markers in the majority of studies. Intravenous BPs are known to cause acute phase reactions leading to flu-like illness following their first infusion, which can be ameliorated by oral acetaminophen. Alendronate is the only oral BP used in these patients. It needs to be taken on an empty stomach with a full glass of water to avoid esophagitis. The side-effects and contraindications to BPs should be kept in mind while treating acute CF patients with them.

The Bisphosphonate Clodronate Modifying Hydroxyapatite Bioceramics for Bone Scaffold

To investigate the efficiency of clodronate modifying HA bioceramics,and to evaluate the effect of clodronate modifying HA bioceramics on the cells in vitro,clodronate modified the porous HA bioceramics for bone scaffold by chelation .The outermost layer of the specimens was analyzd by XPS and FI-IR ,The depth profile was investigated by the argon-ion sputtering method.The cell culture test was conducted using MC3T3-E1 osteoblastic cells,The cells were inoculated and cultured on the scaffolds.Morphological observation of the cells,MTT test and ALP activity test evaluated the cell attachment ,proliferation and activity on the scaffolds.The cell culture test in cell quantity and morphology indicated active proliferation of the cells on the scaffolds.The ALP activity of the cells cultured for 3d and 7d on clodronate-HA bioceramics was slightly higher than that on HA bioceramics ,but the difference was not signifcant,This result indicated that clodronate-HA bioeramics had favorable cytocompatibility to be used as bone scaffold with potential ability to improve asteogensis.

Bisphosphonate use and gastrointestinal tract cancer risk:Meta-analysis of observational studies

AIM:To perform a meta-analysis of observational studies to further elucidate the relationship between oral bisphosphonate use and gastrointestinal cancer risk.METHODS:Systematic literature search was conducted in MEDLINE,EMBASE,and the Cochrane Library to identify studies through January 2011.Search terms were "bisphosphonates" or trade names of the drugs,and "observational studies" or "cohort studies" or "case-control studies".Two evaluators reviewed and selected articles on the basis of predetermined selection criteria as followed:(1) observational studies(casecontrol or cohort studies) on bisphosphonate use;(2) with at least 2 years of follow-up;and(3) reported data on the incidence of cancer diagnosis.The DerSimonian and Laird random effects model were used to calculate the pooled relative risk(RR) with 95% confidence interval(CI).Two-by-two contingency table was used to calculate the outcomes not suitable for meta-analysis.Subgroup meta-analyses were conducted for the type of cancer(esophageal,gastric and colorectal cancers).Sensitivity analyses were performed to examine the effect sizes when only studies with long-term follow-up(mean 5 years;subgroup 3 years) were included.RESULTS:Of 740 screened articles,3 cohort studies and 3 case-control studies were included in the analyses.At first,4 cohort studies and 3 case-control studies were selected for the analyses but one cohort study was excluded because the cancer outcomes were not categorized by type of gastrointestinal cancer.More than 124 686 subjects participated in the 3 cohort studies.The mean follow-up time in all of the cohort studies combined was approximately 3.88 years.The 3 casecontrol studies reported 3070 esophageal cancer cases and 15 417 controls,2018 gastric cancer cases and 10 007 controls,and 11 574 colorectal cancer cases and 53 955 controls.The percentage of study participants who used bisphosphonate was 2.8% among the cases and 2.9% among the controls.The meta-analysis of all the studies found no significant association between bisphosphonate use and gastrointestinal cancer.Also no statistically significant association was found in a meta-analysis of long-term follow-up studies.There was no negative association between bisphosphonate use and the incidence of esophageal cancer in the overall analysis(RR 0.96,95% CI:0.65-1.42,I 2 = 52.8%,P = 0.076) and no statistically significant association with long-term follow-up(RR 1.74,95% CI:0.97-3.10,I 2 = 58.8%,P = 0.119).No negative association was found in the studies reporting the risk of gastric cancer(RR 0.89,95% CI:0.71-1.13,I 2 = 0.0%,P = 0.472).In case of colorectal cancer,there was no association between colorectal cancer and bisphosphonate use(RR 0.62,95% CI:0.30-1.29,I 2 = 88.0%,P = 0.004) and also in the analysis with long-term follow-up(RR 0.61,95% CI:0.28-1.35,I 2 = 84.6%,P = 0.011).CONCLUSION:Oral bisphosphonate use had no significant effect on gastrointestinal cancer risk.However,this finding should be validated in randomized controlled trials with long-term follow-up.

Current concepts in the management of bisphosphonate associated atypical femoral fractures

Bisphosphonates are a class of drugs used as the mainstay of treatment for osteoporosis.Bisphosphonates function by binding to hydroxyapatite,and subsequently targeting osteoclasts by altering their ability to resorb and remodel bone.Whilst aiming to reduce the risk of fragility fractures,bisphosphonates have been associated with atypical insufficiency fractures,specifically in the femur.Atypical femoral fractures occur distal to the lesser trochanter,until the supracondylar flare.There are a number of the differing clinical and radiological features between atypical femoral fractures and osteoporotic femoral fractures,indicating that there is a distinct difference in the respective underlying pathophysiology.At the point of presentation of an atypical femoral fracture,bisphosphonate should be discontinued.This is due to the proposed inhibition of osteoclasts and apoptosis,resulting in impaired callus healing.Conservative management consists primarily of cessation of bisphosphonate therapy and partial weightbearing activity.Nutritional deficiencies should be investigated and appro-priately corrected,most notably dietary calcium and vitamin D.Currently there is no established treatment guidelines for either complete or incomplete fractures.There is agreement in the literature that nonoperative management of bisphosphonate-associated femoral fractures conveys poor outcomes.Currently,the favoured methods of surgical fixation are cephalomedullary nailing and plate fixation.Newer techniques advocate the use of both modalities as it gives the plate advantage of best reducing the fracture and compressing the lateral cortex,with the support of the intramedullary nail to stabilise an atypical fracture with increased ability to load-share,and a reduced bending moment across the fracture site.The evidence suggests that cephalomedullary nailing of the fracture has lower revision rates.However,it is important to appreciate that the anatomical location and patient factors may not always allow for this.Although causation between bisphosphonates and atypical fractures is yet to be demonstrated,there is a growing evidence base to suggest a higher incidence to atypical femoral fractures in patients who take bisphosphonates.As we encounter a growing comorbid elderly population,the prevalence of this fracture-type will likely increase.Therefore,it is imperative clinicians continue to be attentive of atypical femoral fractures and treat them effectively.

Bisphosphonates as potential adjuvants for patients withcancers of the digestive system

Best known for their anti-resorptive activity in bone, bisphosphonates(BPs) have generated interest as potential antineoplastic agents given their pleiotropic biological effects which include antiproliferative, antiangiogenic and immune-modulating properties. Clinical studies in multiple malignancies suggest that BPs may be active in the prevention or treatment of cancer. Digestive tract malignancies represent a large and heterogeneous disease group, and the activity of BPs in these cancers has not been extensively studied. Recent data showing that some BPs inhibit human epidermal growth factor receptor(HER) signaling highlight a potential therapeutic opportunity in digestive cancers, many of which have alterations in the HER axis. Herein, we review the available evidence providing a rationale for the repurposing of BPs as a therapeutic adjunct in the treatment of digestive malignancies, especially in HER-driven subgroups.

Clinical Analysis of Bisphosphonates Treatment on Bone Metastases and Hypercalcemia of Malignancy in Advanced Solid Tumor

Objective： To evaluate the efficacy and toleration of bisphosphonates therapy in patients with bone metastases and hypercalcemia of malignancy in advanced solid tumor. Methods： Patients with histologically or cytologically confirmed cancer and hypercalcemia with bone metastases were designed to open treatment with either 4mg zoledronic acid or 90mg pamidronate. The primary efficacy parameters were pain scores（NRS）, Corrected serum calcium（CSC） and CSC effective rate The vital signs, biochemical and hematological parameters were determined. Results： Twenty patients were enrolled in this study, twelve patients in zoledronic acid group and eight in pamidronate group. Zoledronic acid and pamidronate significantly palliated pain. Pain scores were significantly lower at end-point after Zoledronic acid or pamidronate infusion（5.92 vs 3.25, P〈0.01; 6.13 vs 4.38, P〈0.01, respectively）. The mean CSC level decreased significantly after Zoledronic acid or pamidronate infusion from 12.86 to 10.28mg/dl and 13.19 to 10.36mg/dl respectively. The CSC effective rate was about 90% at 14 days after infusion in two groups. There was no statistical significance for all primary efficacy parameters in zoledronic acid group compared with pamidronate group. An adverse reaction was mild fever after pamidronate infusion and then completely reversible. Conclusion： Zoledronic acid and pamidronate disodium were well tolerated and effective for bone metastases and hypercalcemia of malignancy in advanced solid tumor.

Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw

Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate（BP）-related osteonecrosis of the jaw（ONJ） or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts（n530）; patients with periodontal disease without a history of BP therapy（Control, n510）, patients with periodontal disease having history of BP therapy but without ONJ（BP, n55） and patients with BRONJ（BRONJ, n515）. Denaturing gradient gel electrophoresis of polymerase chain reaction（PCR）-amplified 16 S r RNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ（71.6%）, BP（70.3%） and Control（59.1%）. Significant differences（P,0.05） in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay（ELISA）results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix–loop–helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.

Bisphosphonates Zoledronate and Alendronate for the Management of Postmenopausal Osteoporosis

Bisphosphonates are among the most frequently used antiresorptive drugs for the management of postmenopausal osteoporosis. We review here two of the commonly used bisphosphonates zoledronate and alendronate.

Physicians' knowledge and attitude regarding bisphosphonates-related adverse events:An observational study

AIM To assess the knowledge and attitude of Lebanese physicians regarding bisphosphonates(BPs)-related complications.METHODS An observational cross-sectional study was conducted at a major tertiary teaching hospital in Beirut city,and its affiliated primary health care center.Data were collected through a new self-administered questionnaire distributed via a delegated secretary to physicians expected to regularly prescribe BPs(n = 215).It assessed participants' knowledge,fear and experience regarding BPsreported complications.RESULTS One hundred and fifty-seven physicians fulfilled the questionnaire(response rate: 73.0%): 77.7% and 75.2% considered that gastrointestinal intolerance and osteonecrosis of the jaw are linked to BPs,respectively.Conversely,the least recognised complications are ocular inflammation(7.6%) and severe musculoskeletal pain(37.6%).The association of BPs with oesophageal cancer,atrial fibrillation and hepatotoxicity was reported by 11.5%,13.4% and 24.8% of respondents,respectively.The multivariate analysis showed a significant association between level of knowledge and physicians' department affiliation(P-value = 0.043),their gender(P-value = 0.044),whether or not they prescribe a BP(P-value = 0.012),and the number of BP prescriptions delivered monthly(P-value = 0.012).Physicians are mainly concerned about osteonecrosis of the jaw and nephrotoxicity when prescribing a BP.Yet,the complications commonly met in their practice are gastrointestinal intolerance(44.6%) and acute phase reactions(26.7%).CONCLUSION This study revealed the presence of a deficient knowledge regarding BPs-related adverse events among our physicians.Professional training proposals are needed to increase their knowledge and improve their practices.Pharmaceutical industries should reconsider the instructions they provide to physicians regarding the complications of medications they promote.Moreover,they must actively collaborate with education providers and institutions in educational interventions.

Recurrent Transient Osteoporosis during Pregnancy and Treatment with Oral Bisphosphonates: A Case Report

Transient osteoporosis of the hip (TOH), also known as “Bone marrow edema Syndrome”, is a rare disorder mainly affecting pregnant women in their third trimester, as well as middle-aged, overweight men. A 30-year-old Caucasian female G2P2, with history of transient osteoporosis of both ankles and C-Section during the last pregnancy in 2011, presented progressively severe bilateral hip pain with onset already in the 12th gestational week. Imaging of the pelvis and bilateral hips with MRI obtained 6 days after the C-Section demonstrated bilateral bone-marrow edema of the hips. The patient was treated with a monthly single dose of 150 mg ibandronate acid per os, for 3 months and physiotherapy. Repeated MRI performed 5 months postpartum revealed a complete remission of the disease. In contrast to the first onset of transient osteoporosis during the first pregnancy, which was only treated conservatively without bisphosphonates, the remission of the disease and patient’s recovery with oral ibandronate therapy showed to be 4 months shorter. This case is unique in literature for both describing the onset of this rare disease twice in the same patient as well as its oral therapeutic approach.

An Efficient Synthesis of Aromatic 1-Hydroxymethylene-1, 1-bisphosphonates from Aldehydes

A simple and efficient procedure for synthesis of 1-hydroxymethylene-1,1-bisphos- phoates from aldehydes is described. This method was applied to the synthesis of novel catechol substituted bisphosphonates as the anti-osteoporosis agents.

Determination of bisphosphonates anti-resorptive properties based on three forms of ceramic materials: Sorption and release process evaluation

There is a strong need to search for more effective compounds with bone anti-resorptive properties,which will cause fewer complications than commonly used bisphosphonates. To achieve this goal, it is necessary to search for new techniques to characterize the interactions between bone and drug. By studying their interaction with hydroxyapatite(HA), this study used three forms of ceramic materials,two of which are bone-stimulating materials, to assess the suitability of new active substances with antiresorptive properties. In this study, three methods based on HA in loose form, polycaprolactone/HA(a polymer-ceramic materials containing HA), and polymer-ceramic monolithic in-needle extraction(MINE) device(a polymer inert skeleton), respectively, were used. The affinity of risedronate(a standard compound) and sixteen aminomethylenebisphosphonates(new compounds with potential antiresorptive properties) to HA was defined according to the above-mentioned methods. Ten monolithic materials based on 2-hydroxyethyl methacrylate/ethylene dimethacrylate are prepared and studied, of which one was selected for more-detailed further research. Simulated body fluids containing bisphosphonates were passed through the MINE device. In this way, sorptionedesorption of bisphosphonates was evaluated using this MINE device. The paper presents the advantages and disadvantages of each technique and its suitability for assessing new active substances. All three methods allow for the selection of several compounds with potentially higher anti-resorptive properties than risedronate, in hope that it reflects their higher bone affinity and release ability.

Catechol-Bisphosphonate Conjugates: New Potential Chelating Agents for Metal Intoxication Therapy

In a quest for better chelating therapy drugs for the treatment of intoxication by Fe, Al, oractinides, two new series of mixed catechol-bisphosphonate through amide linkage were synthesized.Benzyl group was used as protecting group to avoid the breakage of amide by acid hydrolysis orimcomplete reaction in silylation-dealkylation using bromotrimethylsilane.

How Long to Treat with Bisphosphonates?

Bisphosphonate class of drugs, the most commonly prescribed for the treatment of osteoporosis, is effective in preventing and treating bone loss and fractures. However, the treatment duration and the applicability of “drug holidays” for bisphosphonates need optimization in order to minimize long-term exposure. Drug holidays may prevent potential adverse events while still maintaining some degree of antifracture efficacy via residual antiresorptive activity by retained bisphosphonates. Patients receiving bisphosphonates, who are at low-moderate risk of fracture, are potential candidates for a drug holiday. However, for high-risk patients or patients with previous history of fragility fractures, the benefits of continuing bisphosphonate therapy considerably out-weigh their potential harm. Evidence-based guidelines regarding starting and stopping a drug holiday are not available;therefore, it is appropriate to monitor patients on a drug holiday to assess a declining antiresorptive effect. In case of a significant rise in bone turnover markers or significant decrease in bone mineral density, it may be time to restart therapy.

A candidate identification questionnaire for postmenopausal osteoporosis patients switched from daily or weekly bisphosphonate to once-monthly ibandronate: An open, prospective, multicenter study—BONCURE study

A candidate identification questionnaire (CIQ) was tested to determine its predictive value for patient-reported satisfaction in patients switched from once-weekly or once-daily treatment with a bisphosphonate to once-monthly dosing. This was a prospective, open-label, multicenter international study in patients with postmenopausal osteoporosis who had been receiving once-daily or once-weekly alendronate or risendronate for at least 3 months. Patients completed a CIQ, then commenced 150 mg monthly ibandronate for 6 months. Patients completed the Osteoporosis Patient Satisfaction Questionnaire (OPSAT-QTM) at baseline for 6 months. Scores were converted to composite satisfaction scores (CSS, scale 0-100). Totally 677 patients completed a CIQ, 645 were enrolled in the treatment phase and comprised the intent-to-treat (ITT) population, and 630 completed the study. In the ITT population, 68.1% patients answered “yes” to one or more CIQ questions. OPSAT-Q scores increased for the convenience, quality of life and overall satisfaction domains (p scores for the side effects domains were significant (p < 0.001) in the CIQ “yes” group, but not for the degree of bother (decrease in mean of 0.1 points, p = 0.50) or duration (no change, p = 0.84) of non-gastrointestinal side effects. Of 638 patients who completed the preference questionnaire, 93.0% of patients preferred the once-monthly dosing schedule and 563 patients (90.7%) found it more convenient. The most common adverse events were dyspepsia (1.9%), nausea (1.1%), and upper abdominal pain (0.9%). Patients are likely to prefer treatment with monthly ibandronate to a weekly or monthly bisphosphonate irrespective of their stated preference before switching treatment.

Effect of Bisphosphonate on Osteoclast of Bone

Bisphosphonates are synthetic analogues of naturally occurring pyrophosphate molecule and are potent inhibitors of osteoclastic bone resorption. Bisphosphonates bind to hydroxyapatite crystals with high affinity and after incorporation by osteoclasts, the primary target cell, it inhibits osteoclastic bone resorption. The anti-resorptive effect has been shown to occur in organ culture as well as in-vivo, but the precise mechanism by which it exerts its bone resorbing effect is not yet fully understood. In vitro and in vivo studies have demonstrated that zoledronate is a more potent inhibitor of osteoclasts than earlier bisphosphonates. Bisphosphonates have now emerged as a leading therapeutic agent for the treatment of hypercalcaemia of malignancy, bone metabolic diseases, Paget’s disease and postmenopausal osteoporosis.

Long Term Outcome of Bisphosphonate Therapy in Patients with Primary Hyperparathyroidism

Context: Primary hyperparathyroidism (PHPT) is commonly associated with reduced bone mineral density (BMD) presenting with osteoporosis, increasing the risk of bone fragility fractures in these patients. Bisphosphonates, due to their anti-resorptive action, are known to improve the BMD and reduce the risk of bone fragility fractures. Therefore, bisphosphonates are considered as an alternative to surgical treatment in managing osteoporosis in PHPT patients. Aim: The aim of this observational study was to assess the effect of long term bisphosphonate therapy on BMD, bone fragility fracture and biochemical markers of bone metabolism in patients with PHPT. Methodology: Fifty patients (mean age 74 years) with PHPT who were treated with long term bisphosphonate therapy were studied retrospectively. The mean baseline (before commencing bisphosphonate therapy) BMD T-scores for lumbar spine (L2-L4) and left femoral neck were -2.5 and -2.1, respectively. Fourteen patients had bone fragility fractures before initiation of bisphosphonate therapy. Results: After an average of 5 years of bisphosphonate treatment, there was a significant increase in lumbar BMD T-score (-2.5 to -2.1, p = 0.013) and a non-significant change in left femoral neck BMD T-score (-2.1 to -2.2, p = 0.497). There was no increase in bone fragility fracture rate (p = 0.167). Serum corrected calcium reduced from 2.74 mmol/L to 2.60 mmol/L (p 0.001) and urine calcium to creatinine ratio from 0.70 to 0.55 (p 0.0001), both within the reference range. Conclusions: Our study suggests that long term bisphosphonate therapy improves lumbar BMD and prevents increase in bone fragility fracture rate. Additionally it improves hypercalcaemia in PHPT.